Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention
Abstract
:1. Introduction
2. Mechanisms of Dormancy Induction and Maintenance
2.1. Intrinsic Mechanisms
2.1.1. Genetic Alterations
2.1.2. Mechanisms of Mammalian Autophagy in Cancer Dormancy
2.1.3. Intracellular Signals
2.1.4. Epigenetic Mechanisms
2.2. Tumor Microenvironment
2.2.1. Extracellular Matrix (ECM)
2.2.2. Hypoxia and Angiogenesis
2.2.3. Immune System
3. Escape from Dormancy
Mechanisms that Sustain Dormancy | ||||
---|---|---|---|---|
Factor | Mechanism | Cancer Type | Metastatic Site | Reference |
Fbxw7 | Cell cycle control | Breast | Lung | [25] |
LIFR | Hypoxia | Breast | Bone Marrow | [26] |
PRRX1 | EMT | HNSCC | Lymph Nodes | [27] |
KISS 1 | Hormone Regulation | Melanoma, Breast, Ovarian | Lung, Intraperitoneal sites | [29] |
Wnt5a | Development | Prostate | Bone | [45] |
IKKβ | Inflammation | Breast | Multiple Sites | [46] |
NR2F1/NANOG | Development, Differentiation | Prostate, HNSCC | Bone Marrow | [50] |
MSK1 | Differentiation | Breast | Bone | [52] |
TGF-β2 | Development, Morphogenesis | HNSCC | Bone Marrow | [58] |
IFN-γ | Immune Response | Sarcoma | Multiple Sites | [79] |
Mechanisms that Promote Escape from Dormancy | ||||
Factor | Mechanism | Cancer Type | Metastatic Site | Reference |
VEGF-A | Angiogenesis | Melanoma, Lung | Brain | [71] |
TSP-1 | ECM constituent | Breast | Bone Marrow | [97] |
MMP-9 | Metabolic Processes | Breast | Brain | [106] |
Coco | Morphogenesis | Breast | Lung | [117] |
VCAM-1 | Cell adhesion | Breast | Lung/Bone | [119] |
4. Therapeutic Implications of Tumor Dormancy/Treatment Strategies
4.1. Maintaining Tumor Dormancy
4.2. Re-Awakening and Sensitization of Dormant Cells to Therapy
4.3. Direct Targeting of Dormant Cells
4.4. Advances in Targeting DTCs
4.5. Future Therapeutic Interventions
5. Conclusions and Future Perspectives
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Conti, C.J. 14.16—Mechanisms of Tumor Progression. In Comprehensive Toxicology, 2nd ed.; McQueen, C.A., Ed.; Elsevier: Oxford, UK, 2010; pp. 335–347. [Google Scholar] [CrossRef]
- Fidler, I.J. The biology of cancer metastasis. Semin. Cancer Biol. 2011, 21, 71. [Google Scholar] [CrossRef] [PubMed]
- Friberg, S.; Nyström, A. Cancer Metastases: Early Dissemination and Late Recurrences. Cancer Growth Metastasis 2015, 8, 43–49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aguirre-Ghiso, J.A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 2007, 7, 834–846. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goss, P.E.; Chambers, A.F. Does tumour dormancy offer a therapeutic target? Nat. Rev. Cancer 2010, 10, 871–877. [Google Scholar] [CrossRef] [PubMed]
- Hadfield, G. The dormant cancer cell. Br. Med. J. 1954, 2, 607. [Google Scholar] [CrossRef]
- Kareva, I. Escape from tumor dormancy and time to angiogenic switch as mitigated by tumor-induced stimulation of stroma. J. Theor. Biol. 2016, 395, 11–22. [Google Scholar] [CrossRef] [PubMed]
- Rakhra, K.; Bachireddy, P.; Zabuawala, T.; Zeiser, R.; Xu, L.; Kopelman, A.; Fan, A.C.; Yang, Q.; Braunstein, L.; Crosby, E. CD4+ T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 2010, 18, 485–498. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schardt, J.A.; Meyer, M.; Hartmann, C.H.; Schubert, F.; Schmidt-Kittler, O.; Fuhrmann, C.; Polzer, B.; Petronio, M.; Eils, R.; Klein, C.A. Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 2005, 8, 227–239. [Google Scholar] [CrossRef] [Green Version]
- Osisami, M.; Keller, E.T. Mechanisms of metastatic tumor dormancy. J. Clin. Med. 2013, 2, 136–150. [Google Scholar] [CrossRef]
- Furuya, M.; Yonemitsu, Y. Cancer neovascularization and proinflammatory microenvironments. Curr. Cancer Drug Targets 2008, 8, 253–265. [Google Scholar] [CrossRef]
- Fluegen, G.; Avivar-Valderas, A.; Wang, Y.; Padgen, M.R.; Williams, J.K.; Nobre, A.R.; Calvo, V.; Cheung, J.F.; Bravo-Cordero, J.J.; Entenberg, D. Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nat. Cell Biol. 2017, 19, 120–132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pantel, K.; Brakenhoff, R.H.; Brandt, B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer 2008, 8, 329–340. [Google Scholar] [CrossRef] [PubMed]
- Badia-Ramentol, J.; Linares, J.; Gómez-Llonin, A.; Calon, A. Minimal residual disease, metastasis and immunity. Biomolecules 2021, 11, 130. [Google Scholar] [CrossRef] [PubMed]
- Chambers, A.F.; Groom, A.C.; MacDonald, I.C. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2002, 2, 563–572. [Google Scholar] [CrossRef]
- Clevers, H. The cancer stem cell: Premises, promises and challenges. Nat. Med. 2011, 17, 313–319. [Google Scholar] [CrossRef] [PubMed]
- Kleinsmith, L.J.; Pierce, G.B., Jr. Multipotentiality of Single Embryonal Carcinoma Cells. Cancer Res. 1964, 24, 1544–1551. [Google Scholar]
- Risson, E.; Nobre, A.R.; Maguer-Satta, V.; Aguirre-Ghiso, J.A. The current paradigm and challenges ahead for the dormancy of disseminated tumor cells. Nat. Cancer 2020, 1, 672–680. [Google Scholar] [CrossRef]
- Damen, M.P.F.; van Rheenen, J.; Scheele, C. Targeting dormant tumor cells to prevent cancer recurrence. FEBS J. 2021, 288, 6286–6303. [Google Scholar] [CrossRef]
- Pisco, A.O.; Brock, A.; Zhou, J.; Moor, A.; Mojtahedi, M.; Jackson, D.; Huang, S. Non-Darwinian dynamics in therapy-induced cancer drug resistance. Nat. Commun. 2013, 4, 2467. [Google Scholar] [CrossRef] [Green Version]
- Saleh, T.; Tyutyunyk-Massey, L.; Gewirtz, D.A. Tumor Cell Escape from Therapy-Induced Senescence as a Model of Disease Recurrence after Dormancy. Cancer Res. 2019, 79, 1044–1046. [Google Scholar] [CrossRef]
- Sutton, M.N.; Yang, H.; Huang, G.Y.; Fu, C.; Pontikos, M.; Wang, Y.; Mao, W.; Pang, L.; Yang, M.; Liu, J.; et al. RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells. Autophagy 2018, 14, 637–653. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neophytou, C.M.; Kyriakou, T.C.; Papageorgis, P. Mechanisms of Metastatic Tumor Dormancy and Implications for Cancer Therapy. Int. J. Mol. Sci. 2019, 20, 6158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sosa, M.S.; Bragado, P.; Aguirre-Ghiso, J.A. Mechanisms of disseminated cancer cell dormancy: An awakening field. Nat. Rev. Cancer 2014, 14, 611–622. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, H.; Takeishi, S.; Nakatsumi, H.; Nakayama, K.I. Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells. JCI Insight 2019, 4, 21. [Google Scholar] [CrossRef] [Green Version]
- Johnson, R.W.; Finger, E.C.; Olcina, M.M.; Vilalta, M.; Aguilera, T.; Miao, Y.; Merkel, A.R.; Johnson, J.R.; Sterling, J.A.; Wu, J.Y.; et al. Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nat. Cell Biol. 2016, 18, 1078–1089. [Google Scholar] [CrossRef] [Green Version]
- Jiang, J.; Zheng, M.; Zhang, M.; Yang, X.; Li, L.; Wang, S.S.; Wu, J.S.; Yu, X.H.; Wu, J.B.; Pang, X.; et al. PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p. Neoplasia 2019, 21, 216–229. [Google Scholar] [CrossRef]
- Lee, J.H.; Welch, D.R. Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Res. 1997, 57, 2384–2387. [Google Scholar]
- Jiang, Y.; Berk, M.; Singh, L.S.; Tan, H.; Yin, L.; Powell, C.T.; Xu, Y. KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha. Clin. Exp. Metastasis 2005, 22, 369–376. [Google Scholar] [CrossRef]
- Vera-Ramirez, L.; Hunter, K.W. Tumor cell dormancy as an adaptive cell stress response mechanism. F1000Res 2017, 6, 2134. [Google Scholar] [CrossRef] [Green Version]
- Lu, Z.; Luo, R.Z.; Lu, Y.; Zhang, X.; Yu, Q.; Khare, S.; Kondo, S.; Kondo, Y.; Yu, Y.; Mills, G.B.; et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J. Clin. Investig. 2008, 118, 3917–3929. [Google Scholar] [CrossRef] [Green Version]
- Shimizu, T.; Sugihara, E.; Yamaguchi-Iwai, S.; Tamaki, S.; Koyama, Y.; Kamel, W.; Ueki, A.; Ishikawa, T.; Chiyoda, T.; Osuka, S.; et al. IGF2 preserves osteosarcoma cell survival by creating an autophagic state of dormancy that protects cells against chemotherapeutic stress. Cancer Res. 2014, 74, 6531–6541. [Google Scholar] [CrossRef] [PubMed]
- Yu, Z.; Zhou, R.; Zhao, Y.; Pan, Y.; Liang, H.; Zhang, J.S.; Tai, S.; Jin, L.; Teng, C.B. Blockage of SLC31A1-dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death. Cell Prolif. 2019, 52, 31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adam, A.P.; George, A.; Schewe, D.; Bragado, P.; Iglesias, B.V.; Ranganathan, A.C.; Kourtidis, A.; Conklin, D.S.; Aguirre-Ghiso, J.A. Computational identification of a p38SAPK-regulated transcription factor network required for tumor cell quiescence. Cancer Res. 2009, 69, 5664–5672. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aguirre-Ghiso, J.A.; Liu, D.; Mignatti, A.; Kovalski, K.; Ossowski, L. Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol. Biol. Cell 2001, 12, 863–879. [Google Scholar] [CrossRef] [Green Version]
- Aguirre-Ghiso, J.A.; Estrada, Y.; Liu, D.; Ossowski, L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 2003, 63, 1684–1695. [Google Scholar] [CrossRef]
- Sosa, M.S.; Avivar-Valderas, A.; Bragado, P.; Wen, H.C.; Aguirre-Ghiso, J.A. ERK1/2 and p38α/β signaling in tumor cell quiescence: Opportunities to control dormant residual disease. Clin. Cancer Res. 2011, 17, 5850–5857. [Google Scholar] [CrossRef] [Green Version]
- Barkan, D.; Kleinman, H.; Simmons, J.L.; Asmussen, H.; Kamaraju, A.K.; Hoenorhoff, M.J.; Liu, Z.Y.; Costes, S.V.; Cho, E.H.; Lockett, S.; et al. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res. 2008, 68, 6241–6250. [Google Scholar] [CrossRef] [Green Version]
- Blows, F.M.; Driver, K.E.; Schmidt, M.K.; Broeks, A.; Van Leeuwen, F.E.; Wesseling, J.; Cheang, M.C.; Gelmon, K.; Nielsen, T.O.; Blomqvist, C. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: A collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010, 7, e1000279. [Google Scholar] [CrossRef]
- Dent, R.; Trudeau, M.; Pritchard, K.I.; Hanna, W.M.; Kahn, H.K.; Sawka, C.A.; Lickley, L.A.; Rawlinson, E.; Sun, P.; Narod, S.A. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin. Cancer Res. 2007, 13, 4429–4434. [Google Scholar] [CrossRef] [Green Version]
- Davies, C.; Pan, H.; Godwin, J.; Gray, R.; Arriagada, R.; Raina, V.; Abraham, M.; Medeiros Alencar, V.H.; Badran, A.; Bonfill, X.; et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013, 381, 805–816. [Google Scholar] [CrossRef] [Green Version]
- Sosnoski, D.M.; Norgard, R.J.; Grove, C.D.; Foster, S.J.; Mastro, A.M. Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment. Clin. Exp. Metastasis 2015, 32, 335–344. [Google Scholar] [CrossRef]
- Carlson, P.; Dasgupta, A.; Grzelak, C.A.; Kim, J.; Barrett, A.; Coleman, I.M.; Shor, R.E.; Goddard, E.T.; Dai, J.; Schweitzer, E.M.; et al. Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy. Nat. Cell Biol. 2019, 21, 238–250. [Google Scholar] [PubMed]
- Freedland, S.J.; Moul, J.W. Prostate specific antigen recurrence after definitive therapy. J. Urol. 2007, 177, 1985–1991. [Google Scholar] [CrossRef] [PubMed]
- Fane, M.E.; Chhabra, Y.; Alicea, G.M.; Maranto, D.A.; Douglass, S.M.; Webster, M.R.; Rebecca, V.W.; Marino, G.E.; Almeida, F.; Ecker, B.L.; et al. Stromal changes in the aged lung induce an emergence from melanoma dormancy. Nature 2022, 606, 396–405. [Google Scholar] [CrossRef] [PubMed]
- El-Shennawy, L.; Dubrovskyi, O.; Kastrati, I.; Danes, J.M.; Zhang, Y.; Whiteley, H.E.; Creighton, C.J.; Frasor, J. Coactivation of Estrogen Receptor and IKKβ Induces a Dormant Metastatic Phenotype in ER-Positive Breast Cancer. Cancer Res. 2018, 78, 974–984. [Google Scholar] [CrossRef] [Green Version]
- Jo, H.; Jia, Y.; Subramanian, K.K.; Hattori, H.; Luo, H.R. Cancer cell-derived clusterin modulates the phosphatidylinositol 3’-kinase-Akt pathway through attenuation of insulin-like growth factor 1 during serum deprivation. Mol. Cell Biol. 2008, 28, 4285–4299. [Google Scholar] [CrossRef] [Green Version]
- Humtsoe, J.O.; Kramer, R.H. Differential epidermal growth factor receptor signaling regulates anchorage-independent growth by modulation of the PI3K/AKT pathway. Oncogene 2010, 29, 1214–1226. [Google Scholar] [CrossRef] [Green Version]
- Robinson, N.J.; Parker, K.A.; Schiemann, W.P. Epigenetic plasticity in metastatic dormancy: Mechanisms and therapeutic implications. Ann. Transl. Med. 2020, 8, 177. [Google Scholar] [CrossRef]
- Sosa, M.S.; Parikh, F.; Maia, A.G.; Estrada, Y.; Bosch, A.; Bragado, P.; Ekpin, E.; George, A.; Zheng, Y.; Lam, H.M.; et al. NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes. Nat. Commun. 2015, 6, 6170. [Google Scholar] [CrossRef] [Green Version]
- Khalil, B.D.; Sanchez, R.; Rahman, T.; Rodriguez-Tirado, C.; Moritsch, S.; Martinez, A.R.; Miles, B.; Farias, E.; Mezei, M.; Nobre, A.R.; et al. An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy. J. Exp. Med. 2022, 219, 23. [Google Scholar] [CrossRef]
- Gawrzak, S.; Rinaldi, L.; Gregorio, S.; Arenas, E.J.; Salvador, F.; Urosevic, J.; Figueras-Puig, C.; Rojo, F.; Del Barco Barrantes, I.; Cejalvo, J.M.; et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat. Cell Biol. 2018, 20, 211–221. [Google Scholar] [CrossRef] [PubMed]
- Linde, N.; Fluegen, G.; Aguirre-Ghiso, J.A. The Relationship Between Dormant Cancer Cells and Their Microenvironment. Adv. Cancer Res. 2016, 132, 45–71. [Google Scholar] [PubMed] [Green Version]
- Butturini, E.; Carcereri de Prati, A.; Boriero, D.; Mariotto, S. Tumor Dormancy and Interplay with Hypoxic Tumor Microenvironment. Int. J. Mol. Sci. 2019, 20, 4305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bichsel, C.A.; Wang, L.; Froment, L.; Berezowska, S.; Müller, S.; Dorn, P.; Marti, T.M.; Peng, R.W.; Geiser, T.; Schmid, R.A.; et al. Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model. Sci. Rep. 2017, 7, 10636. [Google Scholar] [CrossRef]
- Parker, A.L.; Cox, T.R. The Role of the ECM in Lung Cancer Dormancy and Outgrowth. Front. Oncol. 2020, 10, 1766. [Google Scholar] [CrossRef]
- Barney, L.E.; Hall, C.L.; Schwartz, A.D.; Parks, A.N.; Sparages, C.; Galarza, S.; Platt, M.O.; Mercurio, A.M.; Peyton, S.R. Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. Sci. Adv. 2020, 6, eaaz4157. [Google Scholar] [CrossRef] [Green Version]
- Bragado, P.; Estrada, Y.; Parikh, F.; Krause, S.; Capobianco, C.; Farina, H.G.; Schewe, D.M.; Aguirre-Ghiso, J.A. TGF-β2 dictates disseminated tumour cell fate in target organs through TGF-β-RIII and p38α/β signalling. Nat. Cell Biol. 2013, 15, 1351–1361. [Google Scholar] [CrossRef] [Green Version]
- Uhr, J.W.; Pantel, K. Controversies in clinical cancer dormancy. Proc. Natl. Acad. Sci. USA 2011, 108, 12396–12400. [Google Scholar] [CrossRef] [Green Version]
- Milanovic, M.; Fan, D.N.Y.; Belenki, D.; Däbritz, J.H.M.; Zhao, Z.; Yu, Y.; Dörr, J.R.; Dimitrova, L.; Lenze, D.; Monteiro Barbosa, I.A.; et al. Senescence-associated reprogramming promotes cancer stemness. Nature 2018, 553, 96–100. [Google Scholar] [CrossRef] [Green Version]
- Borriello, L.; Coste, A.; Traub, B.; Sharma, V.P.; Karagiannis, G.S.; Lin, Y.; Wang, Y.; Ye, X.; Duran, C.L.; Chen, X.; et al. Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells. Nat. Commun. 2022, 13, 022–28076. [Google Scholar] [CrossRef]
- McNichols, D.W.; Segura, J.W.; DeWeerd, J.H. Renal cell carcinoma: Long-term survival and late recurrence. J. Urol. 1981, 126, 17–23. [Google Scholar] [CrossRef]
- Bliss, S.A.; Sinha, G.; Sandiford, O.A.; Williams, L.M.; Engelberth, D.J.; Guiro, K.; Isenalumhe, L.L.; Greco, S.J.; Ayer, S.; Bryan, M.; et al. Mesenchymal Stem Cell-Derived Exosomes Stimulate Cycling Quiescence and Early Breast Cancer Dormancy in Bone Marrow. Cancer Res. 2016, 76, 5832–5844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qin, R.S.; Zhang, Z.H.; Zhu, N.P.; Chen, F.; Guo, Q.; Hu, H.W.; Fu, S.Z.; Liu, S.S.; Chen, Y.; Fan, J.; et al. Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma. BMC Cancer 2018, 18, 018–4738. [Google Scholar] [CrossRef] [PubMed]
- Indraccolo, S.; Minuzzo, S.; Masiero, M.; Pusceddu, I.; Persano, L.; Moserle, L.; Reboldi, A.; Favaro, E.; Mecarozzi, M.; Di Mario, G.; et al. Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy. Cancer Res. 2009, 69, 1314–1323. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Indraccolo, S. Insights into the regulation of tumor dormancy by angiogenesis in experimental tumors. Adv. Exp. Med. Biol. 2013, 734, 37–52. [Google Scholar] [PubMed]
- Holmgren, L.; O’Reilly, M.S.; Folkman, J. Dormancy of micrometastases: Balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1995, 1, 149–153. [Google Scholar] [CrossRef]
- Ghajar, C.M.; Peinado, H.; Mori, H.; Matei, I.R.; Evason, K.J.; Brazier, H.; Almeida, D.; Koller, A.; Hajjar, K.A.; Stainier, D.Y.; et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 2013, 15, 807–817. [Google Scholar] [CrossRef]
- Gužvić, M.; Klein, C.A. Cancer dormancy: Time to explore its clinical relevance. Breast Cancer Res. 2013, 15, 321. [Google Scholar] [CrossRef] [Green Version]
- Korotchkina, L.G.; Leontieva, O.V.; Bukreeva, E.I.; Demidenko, Z.N.; Gudkov, A.V.; Blagosklonny, M.V. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging 2010, 2, 344–352. [Google Scholar] [CrossRef] [Green Version]
- Panigrahy, D.; Edin, M.L.; Lee, C.R.; Huang, S.; Bielenberg, D.R.; Butterfield, C.E.; Barnés, C.M.; Mammoto, A.; Mammoto, T.; Luria, A.; et al. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J. Clin. Investig. 2012, 122, 178–191. [Google Scholar] [CrossRef] [Green Version]
- Carcereri de Prati, A.; Butturini, E.; Rigo, A.; Oppici, E.; Rossin, M.; Boriero, D.; Mariotto, S. Metastatic Breast Cancer Cells Enter Into Dormant State and Express Cancer Stem Cells Phenotype Under Chronic Hypoxia. J. Cell. Biochem. 2017, 118, 3237–3248. [Google Scholar] [CrossRef] [PubMed]
- Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 2003, 3, 721–732. [Google Scholar] [CrossRef] [PubMed]
- Avivar-Valderas, A.; Bobrovnikova-Marjon, E.; Alan Diehl, J.; Bardeesy, N.; Debnath, J.; Aguirre-Ghiso, J.A. Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK. Oncogene 2013, 32, 4932–4940. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Correa, R.J.; Peart, T.; Valdes, Y.R.; DiMattia, G.E.; Shepherd, T.G. Modulation of AKT activity is associated with reversible dormancy in ascites-derived epithelial ovarian cancer spheroids. Carcinogenesis 2012, 33, 49–58. [Google Scholar] [CrossRef] [PubMed]
- Mittal, D.; Gubin, M.M.; Schreiber, R.D.; Smyth, M.J. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. Curr. Opin. Immunol. 2014, 27, 16–25. [Google Scholar] [CrossRef] [Green Version]
- Farrar, J.D.; Katz, K.H.; Windsor, J.; Thrush, G.; Scheuermann, R.H.; Uhr, J.W.; Street, N.E. Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-gamma in establishing and maintaining the tumor-dormant state. J. Immunol. 1999, 162, 2842–2849. [Google Scholar]
- Eyles, J.; Puaux, A.L.; Wang, X.; Toh, B.; Prakash, C.; Hong, M.; Tan, T.G.; Zheng, L.; Ong, L.C.; Jin, Y.; et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Investig. 2010, 120, 2030–2039. [Google Scholar] [CrossRef]
- Wang, H.F.; Wang, S.S.; Huang, M.C.; Liang, X.H.; Tang, Y.J.; Tang, Y.L. Targeting Immune-Mediated Dormancy: A Promising Treatment of Cancer. Front. Oncol. 2019, 9, 498. [Google Scholar] [CrossRef] [Green Version]
- Saudemont, A.; Quesnel, B. In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Blood 2004, 104, 2124–2133. [Google Scholar] [CrossRef]
- Zou, L.; Barnett, B.; Safah, H.; Larussa, V.F.; Evdemon-Hogan, M.; Mottram, P.; Wei, S.; David, O.; Curiel, T.J.; Zou, W. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004, 64, 8451–8455. [Google Scholar] [CrossRef] [Green Version]
- MacKie, R.M.; Reid, R.; Junor, B. Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N. Engl. J. Med. 2003, 348, 567–568. [Google Scholar] [CrossRef] [PubMed]
- Koebel, C.M.; Vermi, W.; Swann, J.B.; Zerafa, N.; Rodig, S.J.; Old, L.J.; Smyth, M.J.; Schreiber, R.D. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007, 450, 903–907. [Google Scholar] [CrossRef] [PubMed]
- Müller-Hermelink, N.; Braumüller, H.; Pichler, B.; Wieder, T.; Mailhammer, R.; Schaak, K.; Ghoreschi, K.; Yazdi, A.; Haubner, R.; Sander, C.A.; et al. TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 2008, 13, 507–518. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pommier, A.; Anaparthy, N.; Memos, N.; Kelley, Z.L.; Gouronnec, A.; Yan, R.; Auffray, C.; Albrengues, J.; Egeblad, M.; Iacobuzio-Donahue, C.A.; et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases. Science 2018, 360, 17. [Google Scholar] [CrossRef] [Green Version]
- Phan, T.G.; Croucher, P.I. The dormant cancer cell life cycle. Nat. Rev. Cancer 2020, 20, 398–411. [Google Scholar] [CrossRef] [PubMed]
- Johnson, D.B.; Estrada, M.V.; Salgado, R.; Sanchez, V.; Doxie, D.B.; Opalenik, S.R.; Vilgelm, A.E.; Feld, E.; Johnson, A.S.; Greenplate, A.R.; et al. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat. Commun. 2016, 7, 10582. [Google Scholar] [CrossRef] [Green Version]
- Schreeder, D.M.; Cannon, J.P.; Wu, J.; Li, R.; Shakhmatov, M.A.; Davis, R.S. Cutting edge: FcR-like 6 is an MHC class II receptor. J. Immunol. 2010, 185, 23–27. [Google Scholar] [CrossRef] [Green Version]
- Johnson, D.B.; Nixon, M.J.; Wang, Y.; Wang, D.Y.; Castellanos, E.; Estrada, M.V.; Ericsson-Gonzalez, P.I.; Cote, C.H.; Salgado, R.; Sanchez, V.; et al. Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement. JCI Insight 2018, 3, 120360. [Google Scholar] [CrossRef] [Green Version]
- Hemon, P.; Jean-Louis, F.; Ramgolam, K.; Brignone, C.; Viguier, M.; Bachelez, H.; Triebel, F.; Charron, D.; Aoudjit, F.; Al-Daccak, R.; et al. MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J. Immunol. 2011, 186, 5173–5183. [Google Scholar] [CrossRef] [Green Version]
- Casanova-Acebes, M.; Dalla, E.; Leader, A.M.; LeBerichel, J.; Nikolic, J.; Morales, B.M.; Brown, M.; Chang, C.; Troncoso, L.; Chen, S.T.; et al. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells. Nature 2021, 595, 578–584. [Google Scholar] [CrossRef]
- Brodbeck, T.; Nehmann, N.; Bethge, A.; Wedemann, G.; Schumacher, U. Perforin-dependent direct cytotoxicity in natural killer cells induces considerable knockdown of spontaneous lung metastases and computer modelling-proven tumor cell dormancy in a HT29 human colon cancer xenograft mouse model. Mol. Cancer 2014, 13, 1476–4598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, J.; Yao, Y.; Gong, C.; Yu, F.; Su, S.; Liu, B.; Deng, H.; Wang, F.; Lin, L.; Yao, H.; et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell 2011, 19, 541–555. [Google Scholar] [CrossRef] [PubMed]
- Sarmiento-Castro, A.; Caamaño-Gutiérrez, E.; Sims, A.H.; Hull, N.J.; James, M.I.; Santiago-Gómez, A.; Eyre, R.; Clark, C.; Brown, M.E.; Brooks, M.D.; et al. Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH+ Breast Cancer Stem Cells. Stem Cell Rep. 2020, 15, 307–316. [Google Scholar] [CrossRef]
- Willis, R.A. The Spread of Tumors in the Human Body; Butterworth: London, UK, 1952. [Google Scholar]
- Bartosh, T.J.; Ullah, M.; Zeitouni, S.; Beaver, J.; Prockop, D.J. Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs). Proc. Natl. Acad. Sci. USA 2016, 113, E6447–E6456. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qin, X.; Yan, M.; Zhang, J.; Wang, X.; Shen, Z.; Lv, Z.; Li, Z.; Wei, W.; Chen, W. TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis. Sci. Rep. 2016, 6, 20587. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pascual, G.; Avgustinova, A.; Mejetta, S.; Martín, M.; Castellanos, A.; Attolini, C.S.; Berenguer, A.; Prats, N.; Toll, A.; Hueto, J.A.; et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 2017, 541, 41–45. [Google Scholar] [CrossRef] [PubMed]
- Watt, M.J.; Clark, A.K.; Selth, L.A.; Haynes, V.R.; Lister, N.; Rebello, R.; Porter, L.H.; Niranjan, B.; Whitby, S.T.; Lo, J.; et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Sci. Transl. Med. 2019, 11, eaau5758. [Google Scholar] [CrossRef]
- Luo, X.; Cheng, C.; Tan, Z.; Li, N.; Tang, M.; Yang, L.; Cao, Y. Emerging roles of lipid metabolism in cancer metastasis. Mol. Cancer 2017, 16, 017–0646. [Google Scholar] [CrossRef] [Green Version]
- Di Martino, J.S.; Nobre, A.R.; Mondal, C.; Taha, I.; Farias, E.F.; Fertig, E.J.; Naba, A.; Aguirre-Ghiso, J.A.; Bravo-Cordero, J.J. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy. Nat. Cancer 2022, 3, 90–107. [Google Scholar] [CrossRef]
- Lu, X.; Mu, E.; Wei, Y.; Riethdorf, S.; Yang, Q.; Yuan, M.; Yan, J.; Hua, Y.; Tiede, B.J.; Haffty, B.G.; et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell 2011, 20, 701–714. [Google Scholar] [CrossRef] [Green Version]
- Lim, P.K.; Bliss, S.A.; Patel, S.A.; Taborga, M.; Dave, M.A.; Gregory, L.A.; Greco, S.J.; Bryan, M.; Patel, P.S.; Rameshwar, P. Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res. 2011, 71, 1550–1560. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- van den Beucken, T.; Koch, E.; Chu, K.; Rupaimoole, R.; Prickaerts, P.; Adriaens, M.; Voncken, J.W.; Harris, A.L.; Buffa, F.M.; Haider, S.; et al. Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nat. Commun. 2014, 5, 5203. [Google Scholar] [CrossRef] [PubMed]
- Krall, J.A.; Reinhardt, F.; Mercury, O.A.; Pattabiraman, D.R.; Brooks, M.W.; Dougan, M.; Lambert, A.W.; Bierie, B.; Ploegh, H.L.; Dougan, S.K.; et al. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 2018, 10, eaan3464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoskin, P.J. Hypoxia dose painting in prostate and cervix cancer. Acta Oncol. 2015, 54, 1259–1262. [Google Scholar] [CrossRef] [Green Version]
- Albrengues, J.; Shields, M.A.; Ng, D.; Park, C.G.; Ambrico, A.; Poindexter, M.E.; Upadhyay, P.; Uyeminami, D.L.; Pommier, A.; Küttner, V.; et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 2018, 361, eaao4227. [Google Scholar] [CrossRef] [Green Version]
- Johnson, R.W.; Schipani, E.; Giaccia, A.J. HIF targets in bone remodeling and metastatic disease. Pharmacol. Ther. 2015, 150, 169–177. [Google Scholar] [CrossRef] [Green Version]
- Qiu, B.; Simon, M.C. Oncogenes strike a balance between cellular growth and homeostasis. Semin. Cell Dev. Biol. 2015, 43, 3–10. [Google Scholar] [CrossRef] [Green Version]
- Eckers, J.C.; Kalen, A.L.; Sarsour, E.H.; Tompkins, V.S.; Janz, S.; Son, J.M.; Doskey, C.M.; Buettner, G.R.; Goswami, P.C. Forkhead box M1 regulates quiescence-associated radioresistance of human head and neck squamous carcinoma cells. Radiat. Res. 2014, 182, 420–429. [Google Scholar] [CrossRef] [Green Version]
- Bragado, P.; Sosa, M.S.; Keely, P.; Condeelis, J.; Aguirre-Ghiso, J.A. Microenvironments dictating tumor cell dormancy. Recent Results Cancer Res. 2012, 195, 25–39. [Google Scholar]
- Weidenfeld, K.; Schif-Zuck, S.; Abu-Tayeh, H.; Kang, K.; Kessler, O.; Weissmann, M.; Neufeld, G.; Barkan, D. Dormant tumor cells expressing LOXL2 acquire a stem-like phenotype mediating their transition to proliferative growth. Oncotarget 2016, 7, 71362–71377. [Google Scholar] [CrossRef] [Green Version]
- Gammon, L.; Biddle, A.; Heywood, H.K.; Johannessen, A.C.; Mackenzie, I.C. Sub-sets of cancer stem cells differ intrinsically in their patterns of oxygen metabolism. PLoS ONE 2013, 8, e62493. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lawson, M.A.; McDonald, M.M.; Kovacic, N.; Hua Khoo, W.; Terry, R.L.; Down, J.; Kaplan, W.; Paton-Hough, J.; Fellows, C.; Pettitt, J.A.; et al. Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nat. Commun. 2015, 6, 8983. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ottewell, P.D.; Wang, N.; Brown, H.K.; Reeves, K.J.; Fowles, C.A.; Croucher, P.I.; Eaton, C.L.; Holen, I. Zoledronic acid has differential antitumor activity in the pre- and postmenopausal bone microenvironment in vivo. Clin. Cancer Res. 2014, 20, 2922–2932. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Bosch-Marce, M.; Shimoda, L.A.; Tan, Y.S.; Baek, J.H.; Wesley, J.B.; Gonzalez, F.J.; Semenza, G.L. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 2008, 283, 10892–10903. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gammon, L.; Mackenzie, I.C. Roles of hypoxia, stem cells and epithelial-mesenchymal transition in the spread and treatment resistance of head and neck cancer. J. Oral. Pathol. Med. 2016, 45, 77–82. [Google Scholar] [CrossRef]
- Gao, H.; Chakraborty, G.; Lee-Lim, A.P.; Mo, Q.; Decker, M.; Vonica, A.; Shen, R.; Brogi, E.; Brivanlou, A.H.; Giancotti, F.G. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 2012, 150, 764–779. [Google Scholar] [CrossRef] [Green Version]
- Achyut, B.R.; Shankar, A.; Iskander, A.S.; Ara, R.; Angara, K.; Zeng, P.; Knight, R.A.; Scicli, A.G.; Arbab, A.S. Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks. Cancer Lett. 2015, 369, 416–426. [Google Scholar] [CrossRef] [Green Version]
- Meacham, C.E.; Morrison, S.J. Tumour heterogeneity and cancer cell plasticity. Nature 2013, 501, 328–337. [Google Scholar] [CrossRef] [Green Version]
- Puig, I.; Tenbaum, S.P.; Chicote, I.; Arqués, O.; Martínez-Quintanilla, J.; Cuesta-Borrás, E.; Ramírez, L.; Gonzalo, P.; Soto, A.; Aguilar, S.; et al. TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence. J. Clin. Investig. 2018, 128, 3887–3905. [Google Scholar] [CrossRef] [Green Version]
- Wolter, K.; Zender, L. Therapy-induced senescence—An induced synthetic lethality in liver cancer? Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 135–136. [Google Scholar] [CrossRef]
- Recasens, A.; Munoz, L. Targeting Cancer Cell Dormancy. Trends Pharmacol. Sci. 2019, 40, 128–141. [Google Scholar] [CrossRef] [PubMed]
- O’Leary, B.; Finn, R.S.; Turner, N.C. Treating cancer with selective CDK4/6 inhibitors. Nat. Rev. Clin. Oncol. 2016, 13, 417–430. [Google Scholar] [CrossRef] [PubMed]
- Aguirre Ghiso, J.A. Inhibition of FAK signaling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo. Oncogene 2002, 21, 2513–2524. [Google Scholar] [CrossRef]
- El Touny, L.H.; Vieira, A.; Mendoza, A.; Khanna, C.; Hoenerhoff, M.J.; Green, J.E. Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells. J. Clin. Investig. 2014, 124, 156–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barkan, D.; El Touny, L.H.; Michalowski, A.M.; Smith, J.A.; Chu, I.; Davis, A.S.; Webster, J.D.; Hoover, S.; Simpson, R.M.; Gauldie, J.; et al. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 2010, 70, 5706–5716. [Google Scholar] [CrossRef] [Green Version]
- Buczacki, S.J.A.; Popova, S.; Biggs, E.; Koukorava, C.; Buzzelli, J.; Vermeulen, L.; Hazelwood, L.; Francies, H.; Garnett, M.J.; Winton, D.J. Itraconazole targets cell cycle heterogeneity in colorectal cancer. J. Exp. Med. 2018, 215, 1891–1912. [Google Scholar] [CrossRef]
- Liu, Y.; Lv, J.; Liu, J.; Liang, X.; Jin, X.; Xie, J.; Zhang, L.; Chen, D.; Fiskesund, R.; Tang, K.; et al. STAT3/p53 pathway activation disrupts IFN-β-induced dormancy in tumor-repopulating cells. J. Clin. Investig. 2018, 128, 1057–1073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vanner, R.J.; Remke, M.; Gallo, M.; Selvadurai, H.J.; Coutinho, F.; Lee, L.; Kushida, M.; Head, R.; Morrissy, S.; Zhu, X.; et al. Quiescent sox2+ cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma. Cancer Cell 2014, 26, 33–47. [Google Scholar] [CrossRef] [Green Version]
- Achen, M.G.; Stacker, S.A. Molecular control of lymphatic metastasis. Ann. N. Y. Acad. Sci. 2008, 1131, 225–234. [Google Scholar] [CrossRef]
- Saito, Y.; Uchida, N.; Tanaka, S.; Suzuki, N.; Tomizawa-Murasawa, M.; Sone, A.; Najima, Y.; Takagi, S.; Aoki, Y.; Wake, A.; et al. Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat. Biotechnol. 2010, 28, 275–280. [Google Scholar] [CrossRef] [Green Version]
- Essers, M.A.; Offner, S.; Blanco-Bose, W.E.; Waibler, Z.; Kalinke, U.; Duchosal, M.A.; Trumpp, A. IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 2009, 458, 904–908. [Google Scholar] [CrossRef]
- Sleeman, J.P.; Thiele, W. Tumor metastasis and the lymphatic vasculature. Int. J. Cancer 2009, 125, 2747–2756. [Google Scholar] [CrossRef]
- Ewton, D.Z.; Hu, J.; Vilenchik, M.; Deng, X.; Luk, K.C.; Polonskaia, A.; Hoffman, A.F.; Zipf, K.; Boylan, J.F.; Friedman, E.A. Inactivation of mirk/dyrk1b kinase targets quiescent pancreatic cancer cells. Mol. Cancer Ther. 2011, 10, 2104–2114. [Google Scholar] [CrossRef] [PubMed]
- Hiratsuka, S.; Watanabe, A.; Sakurai, Y.; Akashi-Takamura, S.; Ishibashi, S.; Miyake, K.; Shibuya, M.; Akira, S.; Aburatani, H.; Maru, Y. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat. Cell Biol. 2008, 10, 1349–1355. [Google Scholar] [CrossRef] [PubMed]
- Mascré, G.; Dekoninck, S.; Drogat, B.; Youssef, K.K.; Broheé, S.; Sotiropoulou, P.A.; Simons, B.D.; Blanpain, C. Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 2012, 489, 257–262. [Google Scholar] [CrossRef]
- Arosio, A.D.; Pignataro, L.; Gaini, R.M.; Garavello, W. Neck lymph node metastases from unknown primary. Cancer Treat. Rev. 2017, 53, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Staberg, M.; Rasmussen, R.D.; Michaelsen, S.R.; Pedersen, H.; Jensen, K.E.; Villingshøj, M.; Skjoth-Rasmussen, J.; Brennum, J.; Vitting-Seerup, K.; Poulsen, H.S.; et al. Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B. Mol. Oncol. 2018, 12, 406–420. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heinemann, B.; Nielsen, J.M.; Hudlebusch, H.R.; Lees, M.J.; Larsen, D.V.; Boesen, T.; Labelle, M.; Gerlach, L.O.; Birk, P.; Helin, K. Inhibition of demethylases by GSK-J1/J4. Nature 2014, 514, E1–E2. [Google Scholar] [CrossRef]
- Kruidenier, L.; Chung, C.W.; Cheng, Z.; Liddle, J.; Che, K.; Joberty, G.; Bantscheff, M.; Bountra, C.; Bridges, A.; Diallo, H.; et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 2012, 488, 404–408. [Google Scholar] [CrossRef] [Green Version]
- Dalvi, M.P.; Wang, L.; Zhong, R.; Kollipara, R.K.; Park, H.; Bayo, J.; Yenerall, P.; Zhou, Y.; Timmons, B.C.; Rodriguez-Canales, J.; et al. Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors. Cell Rep. 2017, 19, 1669–1684. [Google Scholar] [CrossRef] [Green Version]
- Liau, B.B.; Sievers, C.; Donohue, L.K.; Gillespie, S.M.; Flavahan, W.A.; Miller, T.E.; Venteicher, A.S.; Hebert, C.H.; Carey, C.D.; Rodig, S.J.; et al. Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance. Cell Stem Cell 2017, 20, 233–246. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vinogradova, M.; Gehling, V.S.; Gustafson, A.; Arora, S.; Tindell, C.A.; Wilson, C.; Williamson, K.E.; Guler, G.D.; Gangurde, P.; Manieri, W.; et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat. Chem. Biol. 2016, 12, 531–538. [Google Scholar] [CrossRef] [PubMed]
- Hangauer, M.J.; Viswanathan, V.S.; Ryan, M.J.; Bole, D.; Eaton, J.K.; Matov, A.; Galeas, J.; Dhruv, H.D.; Berens, M.E.; Schreiber, S.L.; et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 2017, 551, 247–250. [Google Scholar] [CrossRef] [PubMed]
- Okada, Y. Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer. Odontology 2010, 98, 153–159. [Google Scholar] [CrossRef]
- Park, S.Y.; Nam, J.S. The force awakens: Metastatic dormant cancer cells. Exp. Mol. Med. 2020, 52, 569–581. [Google Scholar] [CrossRef] [Green Version]
- Shiozawa, Y.; Pedersen, E.A.; Havens, A.M.; Jung, Y.; Mishra, A.; Joseph, J.; Kim, J.K.; Patel, L.R.; Ying, C.; Ziegler, A.M.; et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J. Clin. Investig. 2011, 121, 1298–1312. [Google Scholar] [CrossRef] [Green Version]
- Boyerinas, B.; Zafrir, M.; Yesilkanal, A.E.; Price, T.T.; Hyjek, E.M.; Sipkins, D.A. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood 2013, 121, 4821–4831. [Google Scholar] [CrossRef] [Green Version]
- Ghajar, C.M. Metastasis prevention by targeting the dormant niche. Nat. Rev. Cancer 2015, 15, 238–247. [Google Scholar] [CrossRef]
- Almog, N. Molecular mechanisms underlying tumor dormancy. Cancer Lett. 2010, 294, 139–146. [Google Scholar] [CrossRef]
- Pelicano, H.; Martin, D.S.; Xu, R.H.; Huang, P. Glycolysis inhibition for anticancer treatment. Oncogene 2006, 25, 4633–4646. [Google Scholar] [CrossRef] [Green Version]
- Miller, I.; Min, M.; Yang, C.; Tian, C.; Gookin, S.; Carter, D.; Spencer, S.L. Ki67 is a Graded Rather than a Binary Marker of Proliferation versus Quiescence. Cell Rep. 2018, 24, 1105–1112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khoo, W.H.; Ledergor, G.; Weiner, A.; Roden, D.L.; Terry, R.L.; McDonald, M.M.; Chai, R.C.; De Veirman, K.; Owen, K.L.; Opperman, K.S.; et al. A niche-dependent myeloid transcriptome signature defines dormant myeloma cells. Blood 2019, 134, 30–43. [Google Scholar] [CrossRef] [PubMed]
- Owen, K.L.; Gearing, L.J.; Zanker, D.J.; Brockwell, N.K.; Khoo, W.H.; Roden, D.L.; Cmero, M.; Mangiola, S.; Hong, M.K.; Spurling, A.J.; et al. Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone. EMBO Rep. 2020, 21, 21. [Google Scholar] [CrossRef] [PubMed]
- Dudgeon, C.; Harris, C.R.; Chen, Y.; Ghaddar, B.; Sharma, A.; Shah, M.M.; Roberts, A.I.; Casabianca, A.; Collisson, E.A.; Balachandran, V.P.; et al. A Novel Model of Pancreatic Cancer Dormancy Reveals Mechanistic Insights and a Dormancy Gene Signature with Human Relevance. bioRxiv 2020. [Google Scholar] [CrossRef]
- Kim, R.S.; Avivar-Valderas, A.; Estrada, Y.; Bragado, P.; Sosa, M.S.; Aguirre-Ghiso, J.A.; Segall, J.E. Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. PLoS ONE 2012, 7, e35569. [Google Scholar] [CrossRef] [PubMed]
- Klein, C.A. Cancer progression and the invisible phase of metastatic colonization. Nat. Rev. Cancer 2020, 20, 681–694. [Google Scholar] [CrossRef]
- Naume, B.; Synnestvedt, M.; Falk, R.S.; Wiedswang, G.; Weyde, K.; Risberg, T.; Kersten, C.; Mjaaland, I.; Vindi, L.; Sommer, H.H.; et al. Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. J. Clin. Oncol. 2014, 32, 3848–3857. [Google Scholar] [CrossRef]
- Cox, T.R.; Bird, D.; Baker, A.M.; Barker, H.E.; Ho, M.W.; Lang, G.; Erler, J.T. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res. 2013, 73, 1721–1732. [Google Scholar] [CrossRef] [Green Version]
- Holcomb, I.N.; Grove, D.I.; Kinnunen, M.; Friedman, C.L.; Gallaher, I.S.; Morgan, T.M.; Sather, C.L.; Delrow, J.J.; Nelson, P.S.; Lange, P.H.; et al. Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate cancer patients. Cancer Res. 2008, 68, 5599–5608. [Google Scholar] [CrossRef] [Green Version]
- Hosseini, H.; Obradović, M.M.S.; Hoffmann, M.; Harper, K.L.; Sosa, M.S.; Werner-Klein, M.; Nanduri, L.K.; Werno, C.; Ehrl, C.; Maneck, M.; et al. Early dissemination seeds metastasis in breast cancer. Nature 2016, 540, 552–558. [Google Scholar] [CrossRef] [Green Version]
- Schmidt-Kittler, O.; Ragg, T.; Daskalakis, A.; Granzow, M.; Ahr, A.; Blankenstein, T.J.; Kaufmann, M.; Diebold, J.; Arnholdt, H.; Muller, P.; et al. From latent disseminated cells to overt metastasis: Genetic analysis of systemic breast cancer progression. Proc. Natl. Acad. Sci. USA 2003, 100, 7737–7742. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schumacher, S.; Bartenhagen, C.; Hoffmann, M.; Will, D.; Fischer, J.C.; Baldus, S.E.; Vay, C.; Fluegen, G.; Dizdar, L.; Vallböhmer, D.; et al. Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma. Br. J. Cancer 2017, 117, 725–733. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stoecklein, N.H.; Hosch, S.B.; Bezler, M.; Stern, F.; Hartmann, C.H.; Vay, C.; Siegmund, A.; Scheunemann, P.; Schurr, P.; Knoefel, W.T.; et al. Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer. Cancer Cell 2008, 13, 441–453. [Google Scholar] [CrossRef] [PubMed]
- Weckermann, D.; Polzer, B.; Ragg, T.; Blana, A.; Schlimok, G.; Arnholdt, H.; Bertz, S.; Harzmann, R.; Klein, C.A. Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. J. Clin. Oncol. 2009, 27, 1549–1556. [Google Scholar] [CrossRef] [PubMed]
- Hu, Z.; Ding, J.; Ma, Z.; Sun, R.; Seoane, J.A.; Scott Shaffer, J.; Suarez, C.J.; Berghoff, A.S.; Cremolini, C.; Falcone, A.; et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat. Genet. 2019, 51, 1113–1122. [Google Scholar] [CrossRef] [PubMed]
- Ishaque, N.; Abba, M.L.; Hauser, C.; Patil, N.; Paramasivam, N.; Huebschmann, D.; Leupold, J.H.; Balasubramanian, G.P.; Kleinheinz, K.; Toprak, U.H.; et al. Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. Nat. Commun. 2018, 9, 4782. [Google Scholar] [CrossRef] [Green Version]
- Krøigård, A.B.; Larsen, M.J.; Brasch-Andersen, C.; Lænkholm, A.V.; Knoop, A.S.; Jensen, J.D.; Bak, M.; Mollenhauer, J.; Thomassen, M.; Kruse, T.A. Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence. Sci. Rep. 2017, 7, 43813. [Google Scholar] [CrossRef] [Green Version]
- Cheung, K.J.; Padmanaban, V.; Silvestri, V.; Schipper, K.; Cohen, J.D.; Fairchild, A.N.; Gorin, M.A.; Verdone, J.E.; Pienta, K.J.; Bader, J.S.; et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc. Natl. Acad. Sci. USA 2016, 113, E854–E863. [Google Scholar] [CrossRef] [Green Version]
- Reeves, M.Q.; Kandyba, E.; Harris, S.; Del Rosario, R.; Balmain, A. Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis. Nat. Cell Biol. 2018, 20, 699–709. [Google Scholar] [CrossRef]
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Tamamouna, V.; Pavlou, E.; Neophytou, C.M.; Papageorgis, P.; Costeas, P. Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention. Int. J. Mol. Sci. 2022, 23, 13931. https://doi.org/10.3390/ijms232213931
Tamamouna V, Pavlou E, Neophytou CM, Papageorgis P, Costeas P. Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention. International Journal of Molecular Sciences. 2022; 23(22):13931. https://doi.org/10.3390/ijms232213931
Chicago/Turabian StyleTamamouna, Vasilia, Evangelia Pavlou, Christiana M. Neophytou, Panagiotis Papageorgis, and Paul Costeas. 2022. "Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention" International Journal of Molecular Sciences 23, no. 22: 13931. https://doi.org/10.3390/ijms232213931