Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness
Abstract
Simple Summary
Abstract
1. Introduction
2. Proteoglycans in Brief
3. Proteoglycans as Regulators of EMT and Cell Stemness
3.1. Association of Versican with EMT
3.2. SLRPs: Diverse Regulatory Roles in Cancer Cell Signaling Related to Stemness and EMT
3.3. SPOCK1 Is a Potent Inducer of EMT
3.4. Versatile Functions of Pericellular PGs
3.5. Syndecans: Dual Roles in EMT and Stemness
3.6. Loss of Betaglycan (TGFBR3) Evokes EMT in Cancer Cells
3.7. Glypicans: Contradictory Roles in EMT and cell Stemness
3.8. Serglycin Triggers Oncogenic Signaling and EMT
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AGRN | Agrin |
ASPN | asporin |
BGN | biglycan |
BMP | bone morphogenetic protein |
CAFs | cancer-associated fibroblasts |
CSCs | cancer stem cells |
CS | chondroitin sulfate |
CTGF | connective tissue growth factor |
DCN | decorin |
DS | dermatan sulfate |
EBs | embryoid bodies |
ESCs | embryonic stem cells |
EGFR | epidermal growth factor receptor |
EMP | epithelial mesenchymal plasticity |
EMT | epithelial-to-mesenchymal transition |
ECMs | extracellular matrices |
FGF | fibroblast growth factor |
FOXC2 | forkhead box C2 |
GAGs | glycosaminoglycans |
GPC1 | glypican 1 |
GPC3 | glypican-3 |
GPC4 | glypican-4 |
GPC5 | glypican-5 |
GFs | growth factors |
HCC | hepatocellular carcinoma |
HPSE | heparanase |
HS | heparan sulfate |
HP | heparin |
HA | hyaluronan |
IBC | inflammatory breast cancer |
IGFR-I | insulin-like growth factor receptor I |
ILs | interleukins |
KS | keratan sulfate |
LUM | lumican |
MMPs | matrix metalloproteinases |
MET | mesenchymal-to-epithelial transition |
PRRX1 | paired-related homeobox 1 |
PDGF | platelet-derived growth factor |
PGs | proteoglycans |
SRGN | serglycin |
SLRPs | small leucine-rich proteoglycans |
SDC1 | syndecan-1 |
SDC2 | syndecan-2 |
SDC3 | syndecan 3 |
SDC4 | syndecan 4 |
SPOCK | Testican/SPARC/Osteonectin CWCV and Kazal-like domain |
TGFBR3 | TGFβ receptor III |
TLRs | toll like receptors |
TFs | transcription factors |
TGFβ | transforming growth factor β |
TAMs | tumor-associated macrophages |
TME | tumor microenvironment |
VEGFA | vascular endothelial growth factor A |
VCAN | versican |
ZEB | zinc finger E-box binding homeobox |
References
- Theocharis, A.D.; Manou, D.; Karamanos, N.K. The extracellular matrix as a multitasking player in disease. FEBS J. 2019, 286, 2830–2869. [Google Scholar] [CrossRef] [PubMed]
- Theocharis, A.D.; Skandalis, S.S.; Gialeli, C.; Karamanos, N.K. Extracellular matrix structure. Adv. Drug Deliv. Rev. 2016, 97, 4–27. [Google Scholar] [CrossRef]
- Karamanos, N.K.; Theocharis, A.D.; Piperigkou, Z.; Manou, D.; Passi, A.; Skandalis, S.S.; Vynios, D.H.; Orian-Rousseau, V.; Ricard-Blum, S.; Schmelzer, C.E.H.; et al. A guide to the composition and functions of the extracellular matrix. FEBS J. 2021, 288, 6850–6912. [Google Scholar] [CrossRef]
- Manou, D.; Caon, I.; Bouris, P.; Triantaphyllidou, I.E.; Giaroni, C.; Passi, A.; Karamanos, N.K.; Vigetti, D.; Theocharis, A.D. The Complex Interplay between Extracellular Matrix and Cells in Tissues. Methods Mol. Biol. 2019, 1952, 1–20. [Google Scholar] [PubMed]
- Karamanos, N.K.; Piperigkou, Z.; Theocharis, A.D.; Watanabe, H.; Franchi, M.; Baud, S.; Brezillon, S.; Gotte, M.; Passi, A.; Vigetti, D.; et al. Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics. Chem. Rev. 2018, 118, 9152–9232. [Google Scholar] [CrossRef] [PubMed]
- Theocharis, A.D.; Skandalis, S.S.; Tzanakakis, G.N.; Karamanos, N.K. Proteoglycans in health and disease: Novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J. 2010, 277, 3904–3923. [Google Scholar] [CrossRef] [PubMed]
- Theocharis, A.D.; Karamanos, N.K. Proteoglycans remodeling in cancer: Underlying molecular mechanisms. Matrix Biol. 2019, 75–76, 220–259. [Google Scholar] [CrossRef] [PubMed]
- Scott, L.E.; Weinberg, S.H.; Lemmon, C.A. Mechanochemical Signaling of the Extracellular Matrix in Epithelial-Mesenchymal Transition. Front. Cell Dev. Biol. 2019, 7, 135. [Google Scholar] [CrossRef]
- Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139, 871–890. [Google Scholar] [CrossRef]
- Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol. 2019, 20, 69–84. [Google Scholar] [CrossRef]
- Zhang, Y.; Weinberg, R.A. Epithelial-to-mesenchymal transition in cancer: Complexity and opportunities. Front. Med. 2018, 12, 361–373. [Google Scholar] [CrossRef] [PubMed]
- Brabletz, T.; Kalluri, R.; Nieto, M.A.; Weinberg, R.A. EMT in cancer. Nat. Rev. Cancer 2018, 18, 128–134. [Google Scholar] [CrossRef] [PubMed]
- Solnica-Krezel, L. Conserved Patterns of Cell Movements during Vertebrate Gastrulation. Curr. Biol. 2005, 15, R213–R228. [Google Scholar] [CrossRef] [PubMed]
- Tucker, R.P. Neural crest cells: A model for invasive behavior. Int. J. Biochem. Cell Biol. 2004, 36, 173–177. [Google Scholar] [CrossRef]
- Marconi, G.D.; Fonticoli, L.; Rajan, T.S.; Pierdomenico, S.D.; Trubiani, O.; Pizzicannella, J.; Diomede, F. Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis. Cells 2021, 10, 1587. [Google Scholar] [CrossRef]
- Gonzalez, D.M.; Medici, D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci. Signal. 2014, 7, re8. [Google Scholar] [CrossRef]
- Stemmler, M.P.; Eccles, R.L.; Brabletz, S.; Brabletz, T. Non-redundant functions of EMT transcription factors. Nat. Cell Biol. 2019, 21, 102–112. [Google Scholar] [CrossRef]
- Lambert, A.W.; Weinberg, R.A. Linking EMT programmes to normal and neoplastic epithelial stem cells. Nat. Rev. Cancer 2021, 21, 325–338. [Google Scholar] [CrossRef]
- Ocana, O.H.; Corcoles, R.; Fabra, A.; Moreno-Bueno, G.; Acloque, H.; Vega, S.; Barrallo-Gimeno, A.; Cano, A.; Nieto, M.A. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 2012, 22, 709–724. [Google Scholar] [CrossRef]
- Mani, S.A.; Yang, J.; Brooks, M.; Schwaninger, G.; Zhou, A.; Miura, N.; Kutok, J.L.; Hartwell, K.; Richardson, A.L.; Weinberg, R.A. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc. Natl. Acad. Sci. USA 2007, 104, 10069–10074. [Google Scholar] [CrossRef]
- Cao, Z.; Livas, T.; Kyprianou, N. Anoikis and EMT: Lethal “Liaisons” during Cancer Progression. Crit. Rev. Oncog. 2016, 21, 155–168. [Google Scholar] [CrossRef] [PubMed]
- Gialeli, C.; Theocharis, A.D.; Karamanos, N.K. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011, 278, 16–27. [Google Scholar] [CrossRef] [PubMed]
- Riveline, D.; Zamir, E.; Balaban, N.Q.; Schwarz, U.S.; Ishizaki, T.; Narumiya, S.; Kam, Z.; Geiger, B.; Bershadsky, A.D. Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 2001, 153, 1175–1186. [Google Scholar] [CrossRef] [PubMed]
- Poltavets, V.; Kochetkova, M.; Pitson, S.M.; Samuel, M.S. The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity. Front. Oncol. 2018, 8, 431. [Google Scholar] [CrossRef]
- Xu, H.; Tian, Y.; Yuan, X.; Wu, H.; Liu, Q.; Pestell, R.G.; Wu, K. The role of CD44 in epithelial-mesenchymal transition and cancer development. OncoTargets Ther. 2015, 8, 3783–3792. [Google Scholar]
- McFarlane, S.; McFarlane, C.; Montgomery, N.; Hill, A.; Waugh, D.J. CD44-mediated activation of alpha5beta1-integrin. Cortactin and paxillin signaling underpins adhesion of basal-like breast cancer cells to endothelium and fibronectin-enriched matrices. Oncotarget 2015, 6, 36762–36773. [Google Scholar] [CrossRef]
- Mani, S.A.; Guo, W.; Liao, M.J.; Eaton, E.N.; Ayyanan, A.; Zhou, A.Y.; Brooks, M.; Reinhard, F.; Zhang, C.C.; Shipitsin, M.; et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133, 704–715. [Google Scholar] [CrossRef]
- Domenici, G.; Aurrekoetxea-Rodriguez, I.; Simoes, B.M.; Rabano, M.; Lee, S.Y.; Millan, J.S.; Comaills, V.; Oliemuller, E.; Lopez-Ruiz, J.A.; Zabalza, I.; et al. A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells. Oncogene 2019, 38, 3151–3169. [Google Scholar] [CrossRef]
- Ye, X.; Weinberg, R.A. Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression. Trends Cell Biol. 2015, 25, 675–686. [Google Scholar] [CrossRef]
- De Angelis, M.L.; Francescangeli, F.; Zeuner, A. Breast Cancer Stem Cells as Drivers of Tumor Chemoresistance, Dormancy and Relapse: New Challenges and Therapeutic Opportunities. Cancers 2019, 11, 1569. [Google Scholar] [CrossRef]
- De Angelis, M.L.; Francescangeli, F.; La Torre, F.; Zeuner, A. Stem Cell Plasticity and Dormancy in the Development of Cancer Therapy Resistance. Front. Oncol. 2019, 9, 626. [Google Scholar] [CrossRef] [PubMed]
- Visvader, J.E.; Lindeman, G.J. Cancer stem cells: Current status and evolving complexities. Cell Stem Cell 2012, 10, 717–728. [Google Scholar] [CrossRef] [PubMed]
- Nallanthighal, S.; Heiserman, J.P.; Cheon, D.J. The Role of the Extracellular Matrix in Cancer Stemness. Front. Cell Dev. Biol. 2019, 7, 86. [Google Scholar] [CrossRef] [PubMed]
- Iozzo, R.V.; Schaefer, L. Proteoglycan form and function: A comprehensive nomenclature of proteoglycans. Matrix Biol. 2015, 42, 11–55. [Google Scholar] [CrossRef] [PubMed]
- Theocharis, A.D.; Skandalis, S.S.; Neill, T.; Multhaupt, H.A.; Hubo, M.; Frey, H.; Gopal, S.; Gomes, A.; Afratis, N.; Lim, H.C.; et al. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine. Biochim. Biophys. Acta 2015, 1855, 276–300. [Google Scholar] [CrossRef]
- Afratis, N.A.; Nikitovic, D.; Multhaupt, H.A.; Theocharis, A.D.; Couchman, J.R.; Karamanos, N.K. Syndecans—Key regulators of cell signaling and biological functions. FEBS J. 2017, 284, 27–41. [Google Scholar] [CrossRef]
- Lund, M.E.; Campbell, D.H.; Walsh, B.J. The Role of Glypican-1 in the Tumour Microenvironment. Adv. Exp. Med. Biol. 2020, 1245, 163–176. [Google Scholar]
- Gordon, K.J.; Dong, M.; Chislock, E.M.; Fields, T.A.; Blobe, G.C. Loss of type III transforming growth factor beta receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression. Carcinogenesis 2008, 29, 252–262. [Google Scholar] [CrossRef]
- Korpetinou, A.; Skandalis, S.S.; Labropoulou, V.T.; Smirlaki, G.; Noulas, A.; Karamanos, N.K.; Theocharis, A.D. Serglycin: At the crossroad of inflammation and malignancy. Front. Oncol. 2014, 3, 327. [Google Scholar] [CrossRef]
- Manou, D.; Karamanos, N.K.; Theocharis, A.D. Tumorigenic functions of serglycin: Regulatory roles in epithelial to mesenchymal transition and oncogenic signaling. Semin. Cancer Biol. 2020, 62, 108–115. [Google Scholar] [CrossRef]
- Vasaikar, S.V.; Deshmukh, A.P.; den Hollander, P.; Addanki, S.; Kuburich, N.A.; Kudaravalli, S.; Joseph, R.; Chang, J.T.; Soundararajan, R.; Mani, S.A. EMTome: A resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures. Br. J. Cancer 2021, 124, 259–269. [Google Scholar] [CrossRef] [PubMed]
- Du, W.W.; Fang, L.; Yang, X.; Sheng, W.; Yang, B.L.; Seth, A.; Zhang, Y.; Yang, B.B.; Yee, A.J. The role of versican in modulating breast cancer cell self-renewal. Mol. Cancer Res. 2013, 11, 443–455. [Google Scholar] [CrossRef] [PubMed]
- Oktem, G.; Sercan, O.; Guven, U.; Uslu, R.; Uysal, A.; Goksel, G.; Ayla, S.; Bilir, A. Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids. Oncol. Rep. 2014, 32, 641–649. [Google Scholar] [CrossRef]
- Zhang, Y.; Zou, X.; Qian, W.; Weng, X.; Zhang, L.; Zhang, L.; Wang, S.; Cao, X.; Ma, L.; Wei, G.; et al. Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis. Cell Death Differ. 2019, 26, 565–579. [Google Scholar] [CrossRef]
- Lee, H.C.; Su, M.Y.; Lo, H.C.; Wu, C.C.; Hu, J.R.; Lo, D.M.; Chao, T.Y.; Tsai, H.J.; Dai, M.S. Cancer metastasis and EGFR signaling is suppressed by amiodarone-induced versican V2. Oncotarget 2015, 6, 42976–42987. [Google Scholar] [CrossRef] [PubMed]
- Gao, D.; Vahdat, L.T.; Wong, S.; Chang, J.C.; Mittal, V. Microenvironmental regulation of epithelial-mesenchymal transitions in cancer. Cancer Res. 2012, 72, 4883–4889. [Google Scholar] [CrossRef]
- Sheng, W.; Wang, G.; La Pierre, D.P.; Wen, J.; Deng, Z.; Wong, C.-K.A.; Lee, D.Y.; Yang, B.B. Versican mediates mesenchymal-epithelial transition. Mol. Biol. Cell 2006, 17, 2009–2020. [Google Scholar] [CrossRef][Green Version]
- Soltermann, A.; Tischler, V.; Arbogast, S.; Braun, J.; Probst-Hensch, N.; Weder, W.; Moch, H.; Kristiansen, G. Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin. Cancer Res. 2008, 14, 7430–7437. [Google Scholar] [CrossRef]
- Schulz, G.B.; Grimm, T.; Sers, C.; Riemer, P.; Elmasry, M.; Kirchner, T.; Stief, C.G.; Karl, A.; Horst, D. Prognostic value and association with epithelial-mesenchymal transition and molecular subtypes of the proteoglycan biglycan in advanced bladder cancer. Urol. Oncol. 2019, 37, 530.e9–530.e18. [Google Scholar] [CrossRef]
- Yang, Y.; Wang, R.; Feng, L.; Ma, H.; Fang, J. LINC00460 Promotes Cell Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Head and Neck Squamous Cell Carcinoma via miR-320a/BGN Axis. OncoTargets Ther. 2021, 14, 2279–2291. [Google Scholar] [CrossRef]
- Pinto, F.; Santos-Ferreira, L.; Pinto, M.T.; Gomes, C.; Reis, C.A. The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness. Cancers 2021, 13, 1330. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Zhong, A.; Li, S.; Meng, X.; Wang, X.; Xu, F.; Lai, M. The integrated pathway of TGFβ/Snail with TNFα/NFκB may facilitate the tumor-stroma interaction in the EMT process and colorectal cancer prognosis. Sci. Rep. 2017, 7, 4915. [Google Scholar] [CrossRef]
- Fujiwara-Tani, R.; Sasaki, T.; Fujii, K.; Luo, Y.; Mori, T.; Kishi, S.; Mori, S.; Matsushima-Otsuka, S.; Nishiguchi, Y.; Goto, K.; et al. Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma. Oncotarget 2020, 11, 2982–2994. [Google Scholar] [CrossRef] [PubMed]
- Manupati, K.; Paul, R.; Hao, M.; Haas, M.; Bian, Z.C.; Holm, T.M.; Guan, J.L.; Yeo, S.K. Biglycan Promotes Cancer Stem Cell Properties, NFκB Signaling and Metastatic Potential in Breast Cancer Cells. Cancers 2022, 14, 455. [Google Scholar] [CrossRef] [PubMed]
- Thakur, A.K.; Nigri, J.; Lac, S.; Leca, J.; Bressy, C.; Berthezene, P.; Bartholin, L.; Chan, P.; Calvo, E.; Iovanna, J.L.; et al. TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma. Cell Death Differ. 2016, 23, 1358–1370. [Google Scholar] [CrossRef]
- Xie, C.; Mondal, D.K.; Ulas, M.; Neill, T.; Iozzo, R.V. Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways. Am. J. Physiol. Cell Physiol. 2022, 322, C554–C566. [Google Scholar] [CrossRef]
- Neill, T.; Iozzo, R.V. The Role of Decorin Proteoglycan in Mitophagy. Cancers 2022, 14, 804. [Google Scholar] [CrossRef]
- Basak, D.; Jamal, Z.; Ghosh, A.; Mondal, P.K.; Dey Talukdar, P.; Ghosh, S.; Ghosh Roy, B.; Ghosh, R.; Halder, A.; Chowdhury, A.; et al. Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis. PLoS ONE 2021, 16, e0255915. [Google Scholar] [CrossRef]
- Jia, Y.; Feng, Q.; Tang, B.; Luo, X.; Yang, Q.; Yang, H.; Li, Q. Decorin Suppresses Invasion and EMT Phenotype of Glioma by Inducing Autophagy via c-Met/Akt/mTOR Axis. Front. Oncol. 2021, 11, 659353. [Google Scholar] [CrossRef]
- Hu, X.; Villodre, E.S.; Larson, R.; Rahal, O.M.; Wang, X.; Gong, Y.; Song, J.; Krishnamurthy, S.; Ueno, N.T.; Tripathy, D.; et al. Decorin-mediated suppression of tumorigenesis, invasion, and metastasis in inflammatory breast cancer. Commun. Biol. 2021, 4, 72. [Google Scholar] [CrossRef]
- Zhao, H.; Wang, H.; Kong, F.; Xu, W.; Wang, T.; Xiao, F.; Wang, L.; Huang, D.; Seth, P.; Yang, Y.; et al. Oncolytic Adenovirus rAd.DCN Inhibits Breast Tumor Growth and Lung Metastasis in an Immune-Competent Orthotopic Xenograft Model. Hum. Gene Ther. 2019, 30, 197–210. [Google Scholar] [CrossRef]
- Li, Y.; Hong, J.; Jung, B.K.; Oh, E.; Yun, C.O. Oncolytic Ad co-expressing decorin and Wnt decoy receptor overcomes chemoresistance of desmoplastic tumor through degradation of ECM and inhibition of EMT. Cancer Lett. 2019, 459, 15–29. [Google Scholar] [CrossRef] [PubMed]
- Mao, L.; Yang, J.; Yue, J.; Chen, Y.; Zhou, H.; Fan, D.; Zhang, Q.; Buraschi, S.; Iozzo, R.V.; Bi, X. Decorin deficiency promotes epithelial-mesenchymal transition and colon cancer metastasis. Matrix Biol. 2021, 95, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Simkova, D.; Kharaishvili, G.; Korinkova, G.; Ozdian, T.; Suchankova-Kleplova, T.; Soukup, T.; Krupka, M.; Galandakova, A.; Dzubak, P.; Janikova, M.; et al. The dual role of asporin in breast cancer progression. Oncotarget 2016, 7, 52045–52060. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Wu, H.; Wang, L.; Zhang, H.; Lu, J.; Liang, Z.; Liu, T. Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms. Cancer Lett. 2017, 398, 24–36. [Google Scholar] [CrossRef] [PubMed]
- Simkova, D.; Kharaishvili, G.; Slabakova, E.; Murray, P.G.; Bouchal, J. Glycoprotein asporin as a novel player in tumour microenvironment and cancer progression. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czechoslov. 2016, 160, 467–473. [Google Scholar] [CrossRef] [PubMed]
- Satoyoshi, R.; Kuriyama, S.; Aiba, N.; Yashiro, M.; Tanaka, M. Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene 2015, 34, 650–660. [Google Scholar] [CrossRef]
- Wu, H.; Jing, X.; Cheng, X.; He, Y.; Hu, L.; Wu, H.; Ye, F.; Zhao, R. Asporin enhances colorectal cancer metastasis through activating the EGFR/src/cortactin signaling pathway. Oncotarget 2016, 7, 73402–73413. [Google Scholar] [CrossRef]
- Li, H.; Zhang, Z.; Chen, L.; Sun, X.; Zhao, Y.; Guo, Q.; Zhu, S.; Li, P.; Min, L.; Zhang, S. Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer. Cell Death Dis. 2019, 10, 109. [Google Scholar] [CrossRef]
- Maris, P.; Blomme, A.; Palacios, A.P.; Costanza, B.; Bellahcène, A.; Bianchi, E.; Gofflot, S.; Drion, P.; Trombino, G.E.; Di Valentin, E.; et al. Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer. PLoS Med. 2015, 12, e1001871. [Google Scholar] [CrossRef]
- Karamanou, K.; Franchi, M.; Vynios, D.; Brezillon, S. Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: Lumican a key regulator. Semin. Cancer Biol. 2020, 62, 125–133. [Google Scholar] [CrossRef] [PubMed]
- Giatagana, E.M.; Berdiaki, A.; Tsatsakis, A.; Tzanakakis, G.N.; Nikitovic, D. Lumican in Carcinogenesis-Revisited. Biomolecules 2021, 11, 1319. [Google Scholar] [CrossRef] [PubMed]
- Karamanou, K.; Franchi, M.; Piperigkou, Z.; Perreau, C.; Maquart, F.X.; Vynios, D.H.; Brezillon, S. Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition. Sci. Rep. 2017, 7, 45138. [Google Scholar] [CrossRef] [PubMed]
- Karamanou, K.; Franchi, M.; Onisto, M.; Passi, A.; Vynios, D.H.; Brezillon, S. Evaluation of lumican effects on morphology of invading breast cancer cells, expression of integrins and downstream signaling. FEBS J. 2020, 287, 4862–4880. [Google Scholar] [CrossRef] [PubMed]
- Stasiak, M.; Boncela, J.; Perreau, C.; Karamanou, K.; Chatron-Colliet, A.; Proult, I.; Przygodzka, P.; Chakravarti, S.; Maquart, F.-X.; Kowalska, M.A.; et al. Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity. PLoS ONE 2016, 11, e0150226. [Google Scholar] [CrossRef]
- Karamanou, K.; Franchi, M.; Proult, I.; Rivet, R.; Vynios, D.; Brezillon, S. Lumican Inhibits In Vivo Melanoma Metastasis by Altering Matrix-Effectors and Invadopodia Markers. Cells 2021, 10, 841. [Google Scholar] [CrossRef]
- Wu, J.; Liu, Z.; Shao, C.; Gong, Y.; Hernando, E.; Lee, P.; Narita, M.; Muller, W.; Liu, J.; Wei, J.J. HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes. Cancer Res. 2011, 71, 349–359. [Google Scholar] [CrossRef]
- Farace, C.; Oliver, J.A.; Melguizo, C.; Alvarez, P.; Bandiera, P.; Rama, A.R.; Malaguarnera, G.; Ortiz, R.; Madeddu, R.; Prados, J. Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells. PLoS ONE 2015, 10, e0134111. [Google Scholar]
- Sun, L.R.; Li, S.Y.; Guo, Q.S.; Zhou, W.; Zhang, H.M. SPOCK1 Involvement in Epithelial-to-Mesenchymal Transition: A New Target in Cancer Therapy? Cancer Manag. Res. 2020, 12, 3561–3569. [Google Scholar] [CrossRef]
- Ye, Z.; Chen, J.; Hu, X.; Yang, S.; Xuan, Z.; Lu, X.; Zhao, Q. SPOCK1: A multi-domain proteoglycan at the crossroads of extracellular matrix remodeling and cancer development. Am. J. Cancer Res. 2020, 10, 3127–3137. [Google Scholar]
- Miao, L.; Wang, Y.; Xia, H.; Yao, C.; Cai, H.; Song, Y. SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition. Biochem. Biophys. Res. Commun. 2013, 440, 792–797. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.P.; Han, S.W.; Song, S.H.; Jeong, E.G.; Lee, M.Y.; Hwang, D.; Im, S.A.; Bang, Y.J.; Kim, T.Y. Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene 2014, 33, 3334–3341. [Google Scholar] [CrossRef] [PubMed]
- Zhao, P.; Guan, H.T.; Dai, Z.J.; Ma, Y.G.; Liu, X.X.; Wang, X.J. Knockdown of SPOCK1 Inhibits the Proliferation and Invasion in Colorectal Cancer Cells by Suppressing the PI3K/Akt Pathway. Oncol. Res. 2016, 24, 437–445. [Google Scholar] [CrossRef] [PubMed]
- Cui, X.; Wang, Y.; Lan, W.; Wang, S.; Cui, Y.; Zhang, X.; Lin, Z.; Piao, J. SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α. Cell. Oncol. 2022, 45, 69–84. [Google Scholar] [CrossRef] [PubMed]
- Xu, M.; Zhang, X.; Zhang, S.; Piao, J.; Yang, Y.; Wang, X.; Lin, Z. SPOCK1/SIX1axis promotes breast cancer progression by activating AKT/mTOR signaling. Aging 2020, 13, 1032–1050. [Google Scholar] [CrossRef]
- Fan, L.C.; Jeng, Y.M.; Lu, Y.T.; Lien, H.C. SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer. PLoS ONE 2016, 11, e0162933. [Google Scholar] [CrossRef]
- Song, X.; Han, P.; Liu, J.; Wang, Y.; Li, D.; He, J.; Gong, J.; Li, M.; Tu, W.; Yan, W.; et al. Up-regulation of SPOCK1 induces epithelial-mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma. J. Mol. Histol. 2015, 46, 347–356. [Google Scholar] [CrossRef]
- Chien, M.H.; Lin, Y.W.; Wen, Y.C.; Yang, Y.C.; Hsiao, M.; Chang, J.L.; Huang, H.C.; Lee, W.J. Targeting the SPOCK1-snail/slug axis-mediated epithelial-to-mesenchymal transition by apigenin contributes to repression of prostate cancer metastasis. J. Exp. Clin. Cancer Res. 2019, 38, 246. [Google Scholar] [CrossRef]
- Yu, F.; Li, G.; Gao, J.; Sun, Y.; Liu, P.; Gao, H.; Li, P.; Lei, T.; Chen, Y.; Cheng, Y.; et al. SPOCK1 is upregulated in recurrent glioblastoma and contributes to metastasis and Temozolomide resistance. Cell Prolif. 2016, 49, 195–206. [Google Scholar] [CrossRef]
- Chakraborty, S.; Lakshmanan, M.; Swa, H.L.; Chen, J.; Zhang, X.; Ong, Y.S.; Loo, L.S.; Akincilar, S.C.; Gunaratne, J.; Tergaonkar, V.; et al. An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nat. Commun. 2015, 6, 6184. [Google Scholar] [CrossRef]
- Lv, X.; Fang, C.; Yin, R.; Qiao, B.; Shang, R.; Wang, J.; Song, W.; He, Y.; Chen, Y. Agrin para-secreted by PDGF-activated human hepatic stellate cells promotes hepatocarcinogenesis in vitro and in vivo. Oncotarget 2017, 8, 105340–105355. [Google Scholar] [CrossRef] [PubMed]
- Ruivo, C.F.; Bastos, N.; Adem, B.; Batista, I.; Duraes, C.; Melo, C.A.; Castaldo, S.A.; Campos-Laborie, F.; Moutinho-Ribeiro, P.; Morao, B.; et al. Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression. Gut 2022, 71, 2043–2068. [Google Scholar] [CrossRef] [PubMed]
- Carvalhaes, L.S.; Gervasio, O.L.; Guatimosim, C.; Heljasvaara, R.; Sormunen, R.; Pihlajaniemi, T.; Kitten, G.T. Collagen XVIII/endostatin is associated with the epithelial-mesenchymal transformation in the atrioventricular valves during cardiac development. Dev. Dyn. 2006, 235, 132–142. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Zhang, H.; Zhu, H.; Yang, X.; Yang, Y.; Yang, Y.; Min, H.; Chen, G.; Liu, J.; Lu, J.; et al. Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial-mesenchymal transition in esophageal cancer. Tumour Biol. 2016, 37, 4679–4688. [Google Scholar] [CrossRef] [PubMed]
- Hu, P.; Ma, L.; Wu, Z.Q.; Zheng, G.Y.; Li, J.T. Effect of endostatin on proliferation. invasion and epithelial-mesenchymal transition of basal cell carcinoma cell A431. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 877–884. [Google Scholar]
- Wang, Y.; Jiang, M.; Li, Z.; Wang, J.; Du, C.; Yanyang, L.; Yu, Y.; Wang, X.; Zhang, N.; Zhao, M.; et al. Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors. Cell Biosci. 2015, 5, 72. [Google Scholar] [CrossRef]
- Ding, Y.; Wang, Y.; Cui, J.; Si, T. Endostar blocks the metastasis. invasion and angiogenesis of ovarian cancer cells. Neoplasma 2020, 67, 595–603. [Google Scholar] [CrossRef]
- Shen, Y.; Chen, Q.; Li, L. Endostar regulates EMT. migration and invasion of lung cancer cells through the HGF-Met pathway. Mol. Cell. Probes 2019, 45, 57–64. [Google Scholar] [CrossRef]
- Tian, W.; Li, J.; Wang, Z.; Zhang, T.; Han, Y.; Liu, Y.; Chu, W.; Liu, Y.; Yang, B. HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation. Acta Pharm. Sin. B 2021, 11, 1592–1606. [Google Scholar] [CrossRef]
- Ibrahim, S.A.; Hassan, H.; Vilardo, L.; Kumar, S.K.; Kumar, A.V.; Kelsch, R.; Schneider, C.; Kiesel, L.; Eich, H.T.; Zucchi, I.; et al. Syndecan-1 (CD138) modulates triple-negative breast cancer stem cell properties via regulation of LRP-6 and IL-6-mediated STAT3 signaling. PLoS ONE 2013, 8, e85737. [Google Scholar] [CrossRef]
- Ibrahim, S.A.; Gadalla, R.; El-Ghonaimy, E.A.; Samir, O.; Mohamed, H.T.; Hassan, H.; Greve, B.; El-Shinawi, M.; Mohamed, M.M.; Götte, M. Syndecan-1 Is a Novel Molecular Marker for Triple Negative Inflammatory Breast Cancer and Modulates the Cancer Stem Cell Phenotype via the IL-6/STAT3, Notch and EGFR Signaling Pathways; BioMed Central Ltd.: London, UK, 2017. [Google Scholar]
- Juuti, A.; Nordling, S.; Lundin, J.; Louhimo, J.; Haglund, C. Syndecan-1 expression—A novel prognostic marker in pancreatic cancer. Oncology 2005, 68, 97–106. [Google Scholar] [CrossRef] [PubMed]
- Gharbaran, R. Advances in the molecular functions of syndecan-1 (SDC1/CD138) in the pathogenesis of malignancies. Crit. Rev. Oncol. Hematol. 2015, 94, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Lin, S.C.; Wu, C.P.; Tseng, T.; Jhang, Y.; Lee, S.C. Role of syndecan-1 and exogenous heparin in hepatoma sphere formation. Biochem. Cell Biol. 2020, 98, 112–119. [Google Scholar] [CrossRef] [PubMed]
- Couchman, J.R. Syndecan-1 (CD138), Carcinomas and EMT. Int. J. Mol. Sci. 2021, 22, 4227. [Google Scholar] [CrossRef]
- Loussouarn, D.; Campion, L.; Sagan, C.; Frenel, J.S.; Dravet, F.; Classe, J.M.; Pioud-Martigny, R.; Berton-Rigaud, D.; Bourbouloux, E.; Mosnier, J.F.; et al. Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas. Br. J. Cancer 2008, 98, 1993–1998. [Google Scholar] [CrossRef]
- Masola, V.; Gambaro, G.; Tibaldi, E.; Brunati, A.M.; Gastaldello, A.; D’Angelo, A.; Onisto, M.; Lupo, A. Heparanase and syndecan-1 interplay orchestrates fibroblast growth factor-2-induced epithelial-mesenchymal transition in renal tubular cells. J. Biol. Chem. 2012, 287, 1478–1488. [Google Scholar] [CrossRef]
- Chen, X.; Zhao, H.; Chen, C.; Li, J.; He, J.; Fu, X.; Zhao, H. The HPA/SDC1 axis promotes invasion and metastasis of pancreatic cancer cells by activating EMT via FGF2 upregulation. Oncol. Lett. 2020, 19, 211–220. [Google Scholar] [CrossRef]
- Farfan, N.; Ocarez, N.; Castellon, E.A.; Mejia, N.; de Herreros, A.G.; Contreras, H.R. The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer. Sci. Rep. 2018, 8, 11467. [Google Scholar] [CrossRef]
- Poblete, C.E.; Fulla, J.; Gallardo, M.; Munoz, V.; Castellon, E.A.; Gallegos, I.; Contreras, H.R. Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer. Int. J. Oncol. 2014, 44, 647–654. [Google Scholar] [CrossRef]
- Liu, Z.X.; Jin, H.; Yang, S.; Cao, H.M.; Zhang, Z.Y.; Wen, B.; Zhou, S.B. SDC1 knockdown induces epithelial-mesenchymal transition and invasion of gallbladder cancer cells via the ERK/Snail pathway. J. Int. Med. Res. 2020, 48. [Google Scholar] [CrossRef]
- Wang, X.; He, J.; Zhao, X.; Qi, T.; Zhang, T.; Kong, C. Syndecan-1 suppresses epithelial-mesenchymal transition and migration in human oral cancer cells. Oncol. Rep. 2018, 39, 1835–1842. [Google Scholar] [CrossRef] [PubMed]
- Mitselou, A.; Galani, V.; Skoufi, U.; Arvanitis, D.L.; Lampri, E.; Ioachim, E. Syndecan-1, Epithelial-Mesenchymal Transition Markers (E-cadherin/beta-catenin) and Neoangiogenesis-related Proteins (PCAM-1 and Endoglin) in Colorectal Cancer. Anticancer Res. 2016, 36, 2271–2280. [Google Scholar] [PubMed]
- Zeng, Y.; Yao, X.; Chen, L.; Yan, Z.; Liu, J.; Zhang, Y.; Feng, T.; Wu, J.; Liu, X. Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/syndecan-1/TGF-beta autocrine loop. Oncotarget 2016, 7, 63324–63337. [Google Scholar] [CrossRef] [PubMed]
- Kumar-Singh, A.; Parniewska, M.M.; Giotopoulou, N.; Javadi, J.; Sun, W.; Szatmari, T.; Dobra, K.; Hjerpe, A.; Fuxe, J. Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells. Biology 2021, 10, 521. [Google Scholar] [CrossRef]
- D’Arcy, C.; Zimmermann, C.C.; Espinoza-Sanchez, N.A.; Greve, B.; Schmidt, A.; Kiesel, L.; von Wahlde, M.-K.; Götte, M. The heparan sulphate proteoglycan Syndecan-1 (CD138) regulates tumour progression in a 3D model of ductal carcinoma in situ of the breast. IUBMB Life 2022, 74, 955–968. [Google Scholar] [CrossRef]
- Jang, B.; Jung, H.; Chung, H.; Moon, B.I.; Oh, E.S. Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells. Biochem. Biophys. Res. Commun. 2016, 477, 47–53. [Google Scholar] [CrossRef]
- Jang, B.; Jung, H.; Choi, S.; Lee, Y.H.; Lee, S.T.; Oh, E.S. Syndecan-2 cytoplasmic domain up-regulates matrix metalloproteinase-7 expression via the protein kinase Cgamma-mediated FAK/ERK signaling pathway in colon cancer. J. Biol. Chem. 2017, 292, 16321–16332. [Google Scholar] [CrossRef]
- Hua, R.; Yu, J.; Yan, X.; Ni, Q.; Zhi, X.; Li, X.; Jiang, B.; Zhu, J. Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway. Biomed. Pharmacother. 2020, 121, 109630. [Google Scholar] [CrossRef]
- Ma, N.; Li, X.; Wei, H.; Zhang, H.; Zhang, S. Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2. Cell. Oncol. 2021, 44, 93–107. [Google Scholar] [CrossRef]
- Diamantopoulou, Z.; Kitsou, P.; Menashi, S.; Courty, J.; Katsoris, P. Loss of receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta) promotes prostate cancer metastasis. J. Biol. Chem. 2012, 287, 40339–40349. [Google Scholar] [CrossRef]
- Hillemeyer, L.; Espinoza-Sanchez, N.A.; Greve, B.; Hassan, N.; Chelariu-Raicu, A.; Kiesel, L.; Gotte, M. The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis. Int. J. Mol. Sci. 2022, 23, 5793. [Google Scholar] [CrossRef] [PubMed]
- Keller-Pinter, A.; Gyulai-Nagy, S.; Becsky, D.; Dux, L.; Rovo, L. Syndecan-4 in Tumor Cell Motility. Cancers 2021, 13, 3322. [Google Scholar] [CrossRef] [PubMed]
- Onyeisi, J.O.S.; Lopes, C.C.; Gotte, M. Syndecan-4 as a Pathogenesis Factor and Therapeutic Target in Cancer. Biomolecules 2021, 11, 503. [Google Scholar] [CrossRef] [PubMed]
- Labropoulou, V.T.; Skandalis, S.S.; Ravazoula, P.; Perimenis, P.; Karamanos, N.K.; Kalofonos, H.P.; Theocharis, A.D. Expression of syndecan-4 and correlation with metastatic potential in testicular germ cell tumours. BioMed Res. Int. 2013, 2013, 214864. [Google Scholar] [CrossRef]
- Jechorek, D.; Haeusler-Pliske, I.; Meyer, F.; Roessner, A. Diagnostic value of syndecan-4 protein expression in colorectal cancer. Pathol. Res. Pract. 2021, 222, 153431. [Google Scholar] [CrossRef]
- Toba-Ichihashi, Y.; Yamaoka, T.; Ohmori, T.; Ohba, M. Up-regulation of Syndecan-4 contributes to TGF-beta1-induced epithelial to mesenchymal transition in lung adenocarcinoma A549 cells. Biochem. Biophys. Rep. 2016, 5, 1–7. [Google Scholar]
- Chen, L.L.; Gao, G.X.; Shen, F.X.; Chen, X.; Gong, X.H.; Wu, W.J. SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/beta-Catenin Pathway. Mol. Cells 2018, 41, 853–867. [Google Scholar]
- Ohkawara, B.; Glinka, A.; Niehrs, C. Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis. Dev. Cell 2011, 20, 303–314. [Google Scholar] [CrossRef]
- Liao, W.C.; Yen, H.R.; Chen, C.H.; Chu, Y.H.; Song, Y.C.; Tseng, T.J.; Liu, C.H. CHPF promotes malignancy of breast cancer cells by modifying syndecan-4 and the tumor microenvironment. Am. J. Cancer Res. 2021, 11, 812–826. [Google Scholar]
- Guan, Z.; Sun, Y.; Mu, L.; Jiang, Y.; Fan, J. Tenascin-C promotes bladder cancer progression and its action depends on syndecan-4 and involves NF-kappaB signaling activation. BMC Cancer 2022, 22, 240. [Google Scholar] [CrossRef]
- Gordon, K.J.; Kirkbride, K.C.; How, T.; Blobe, G.C. Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2. Carcinogenesis 2009, 30, 238–248. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S.; Sun, W.Y.; Wu, J.J.; Gu, Y.J.; Wei, W. Decreased expression of the type III TGF-beta receptor enhances metastasis and invasion in hepatocellullar carcinoma progression. Oncol. Rep. 2016, 35, 2373–2381. [Google Scholar] [CrossRef] [PubMed]
- Cheng, C.W.; Hsiao, J.R.; Fan, C.C.; Lo, Y.K.; Tzen, C.Y.; Wu, L.W.; Fang, W.Y.; Cheng, A.J.; Chen, C.H.; Chang, I.S.; et al. Loss of GDF10/BMP3b as a prognostic marker collaborates with TGFBR3 to enhance chemotherapy resistance and epithelial-mesenchymal transition in oral squamous cell carcinoma. Mol. Carcinogen. 2016, 55, 499–513. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Liu, K.; Li, Z.; Wang, J.; Wang, X. miR-19a and miR-424 target TGFBR3 to promote epithelial-to-mesenchymal transition and migration of tongue squamous cell carcinoma cells. Cell Adhes. Migr. 2018, 12, 236–246. [Google Scholar] [CrossRef] [PubMed]
- Xie, L.; Yao, Z.; Zhang, Y.; Li, D.; Hu, F.; Liao, Y.; Zhou, L.; Zhou, Y.; Huang, Z.; He, Z.; et al. Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis. Cell Death Dis. 2018, 9, 772. [Google Scholar] [CrossRef]
- You, H.J.; How, T.; Blobe, G.C. The type III transforming growth factor-β receptor negatively regulates nuclear factor kappa B signaling through its interaction with β-arrestin2. Carcinogenesis 2009, 30, 1281–1287. [Google Scholar] [CrossRef]
- Meyer, A.E.; Gatza, C.E.; How, T.; Starr, M.; Nixon, A.B.; Blobe, G.C. Role of TGF-beta receptor III localization in polarity and breast cancer progression. Mol. Biol. Cell 2014, 25, 2291–2304. [Google Scholar] [CrossRef]
- Li, J.; Li, B.; Ren, C.; Chen, Y.; Guo, X.; Zhou, L.; Peng, Z.; Tang, Y.; Chen, Y.; Liu, W.; et al. The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients. Oncotarget 2017, 8, 101189–101202. [Google Scholar] [CrossRef]
- Papiewska-Pajak, I.; Krzyzanowski, D.; Katela, M.; Rivet, R.; Michlewska, S.; Przygodzka, P.; Kowalska, M.A.; Brezillon, S. Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail. Cells 2020, 9, 1585. [Google Scholar] [CrossRef]
- Li, J.; Chen, Y.; Zhan, C.; Zhu, J.; Weng, S.; Dong, L.; Liu, T.; Shen, X. Glypican-1 Promotes Tumorigenesis by Regulating the PTEN/Akt/beta-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. Dig. Dis. Sci. 2019, 64, 1493–1502. [Google Scholar] [CrossRef]
- Castillo, L.F.; Tascon, R.; Lago Huvelle, M.R.; Novack, G.; Llorens, M.C.; Dos Santos, A.F.; Shortrede, J.; Cabanillas, A.M.; Bal de Kier Joffe, E.; Labriola, L.; et al. Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells. Oncotarget 2016, 7, 60133–60154. [Google Scholar] [CrossRef] [PubMed]
- Qi, X.H.; Wu, D.; Cui, H.X.; Ma, N.; Su, J.; Wang, Y.T.; Jiang, Y.H. Silencing of the glypican-3 gene affects the biological behavior of human hepatocellular carcinoma cells. Mol. Med. Rep. 2014, 10, 3177–3184. [Google Scholar] [CrossRef] [PubMed]
- Guereno, M.; Delgado Pastore, M.; Lugones, A.C.; Cercato, M.; Todaro, L.; Urtreger, A.; Peters, M.G. Glypican-3 (GPC3) inhibits metastasis development promoting dormancy in breast cancer cells by p38 MAPK pathway activation. Eur. J. Cell Biol. 2020, 99, 151096. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Liu, H.; Weng, H.; Zhang, X.; Li, P.; Fan, C.L.; Li, B.; Dong, P.L.; Li, L.; Dooley, S.; et al. Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway. Int. J. Oncol. 2015, 46, 1275–1285. [Google Scholar] [CrossRef]
- Meng, P.; Zhang, Y.F.; Zhang, W.; Chen, X.; Xu, T.; Hu, S.; Liang, X.; Feng, M.; Yang, X.; Ho, M. Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells. Sci. Rep. 2021, 11, 40. [Google Scholar] [CrossRef]
- Fico, A.; De Chevigny, A.; Egea, J.; Bosl, M.R.; Cremer, H.; Maina, F.; Dono, R. Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency. Stem Cells 2012, 30, 1863–1874. [Google Scholar] [CrossRef]
- Vitale, D.; Kumar Katakam, S.; Greve, B.; Jang, B.; Oh, E.S.; Alaniz, L.; Gotte, M. Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance. FEBS J. 2019, 286, 2870–2882. [Google Scholar] [CrossRef]
- Oikari, L.E.; Okolicsanyi, R.K.; Qin, A.; Yu, C.; Griffiths, L.R.; Haupt, L.M. Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination. Stem Cell Res. 2016, 16, 92–104. [Google Scholar] [CrossRef]
- Cao, J.; Ma, J.; Sun, L.; Li, J.; Qin, T.; Zhou, C.; Cheng, L.; Chen, K.; Qian, W.; Duan, W.; et al. Targeting glypican-4 overcomes 5-FU resistance and attenuates stem cell-like properties via suppression of Wnt/beta-catenin pathway in pancreatic cancer cells. J. Cell. Biochem. 2018, 119, 9498–9512. [Google Scholar] [CrossRef]
- Wang, S.; Qiu, M.; Xia, W.; Xu, Y.; Mao, Q.; Wang, J.; Dong, G.; Xu, L.; Yang, X.; Yin, R. Glypican-5 suppresses Epithelial-Mesenchymal Transition of the lung adenocarcinoma by competitively binding to Wnt3a. Oncotarget 2016, 7, 79736–79746. [Google Scholar] [CrossRef]
- Sun, Y.; Xu, K.; He, M.; Fan, G.; Lu, H. Overexpression of Glypican 5 (GPC5) Inhibits Prostate Cancer Cell Proliferation and Invasion via Suppressing Sp1-Mediated EMT and Activation of Wnt/beta-Catenin Signaling. Oncol. Res. 2018, 26, 565–572. [Google Scholar] [CrossRef] [PubMed]
- He, L.; Zhou, X.; Qu, C.; Tang, Y.; Zhang, Q.; Hong, J. Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients. Med. Oncol. 2013, 30, 707. [Google Scholar] [CrossRef] [PubMed]
- Bouris, P.; Manou, D.; Sopaki-Valalaki, A.; Kolokotroni, A.; Moustakas, A.; Kapoor, A.; Iozzo, R.V.; Karamanos, N.K.; Theocharis, A.D. Serglycin promotes breast cancer cell aggressiveness: Induction of epithelial to mesenchymal transition. Proteolytic activity and IL-8 signaling. Matrix Biol. 2018, 74, 35–51. [Google Scholar] [CrossRef]
- Zhang, Z.; Deng, Y.; Zheng, G.; Jia, X.; Xiong, Y.; Luo, K.; Qiu, Q.; Qiu, N.; Yin, J.; Lu, M.; et al. SRGN-TGFbeta2 regulatory loop confers invasion and metastasis in triple-negative breast cancer. Oncogenesis 2017, 6, e360. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Qiu, N.; Yin, J.; Zhang, J.; Liu, H.; Guo, W.; Liu, M.; Liu, T.; Chen, D.; Luo, K.; et al. SRGN crosstalks with YAP to maintain chemoresistance and stemness in breast cancer cells by modulating HDAC2 expression. Theranostics 2020, 10, 4290–4307. [Google Scholar] [CrossRef]
- Xu, Y.; Xu, J.; Yang, Y.; Zhu, L.; Li, X.; Zhao, W. SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1alpha. Cell. Physiol. Biochem. 2018, 48, 2429–2440. [Google Scholar] [CrossRef]
- Guo, J.Y.; Hsu, H.S.; Tyan, S.W.; Li, F.Y.; Shew, J.Y.; Lee, W.H.; Chen, J.Y. Serglycin in tumor microenvironment promotes non-small cell lung cancer aggressiveness in a CD44-dependent manner. Oncogene 2017, 36, 2457–2471. [Google Scholar] [CrossRef]
- Li, X.J.; Ong, C.K.; Cao, Y.; Xiang, Y.Q.; Shao, J.Y.; Ooi, A.; Peng, L.X.; Lu, W.H.; Zhang, Z.; Petillo, D.; et al. Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis. Cancer Res. 2011, 71, 3162–3172. [Google Scholar] [CrossRef]
- Manou, D.; Bouris, P.; Kletsas, D.; Gotte, M.; Greve, B.; Moustakas, A.; Karamanos, N.K.; Theocharis, A.D. Serglycin activates pro-tumorigenic signaling and controls glioblastoma cell stemness, differentiation and invasive potential. Matrix Biol. Plus 2020, 6–7, 100033. [Google Scholar] [CrossRef]
- Tellez-Gabriel, M.; Tekpli, X.; Reine, T.M.; Hegge, B.; Nielsen, S.R.; Chen, M.; Moi, L.; Normann, L.S.; Busund, L.-T.R.; Calin, G.A.; et al. Serglycin Is Involved in TGF-β Induced Epithelial-Mesenchymal Transition and Is Highly Expressed by Immune Cells in Breast Cancer Tissue. Front. Oncol. 2022, 12, 868868. [Google Scholar] [CrossRef]
- Roy, A.; Femel, J.; Huijbers, E.J.; Spillmann, D.; Larsson, E.; Ringvall, M.; Olsson, A.K.; Abrink, M. Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma. PLoS ONE 2016, 11, e0156151. [Google Scholar] [CrossRef] [PubMed]
PG | Localization/Family | Function | Mechanism |
---|---|---|---|
VCAN | Extracellular/Hyalectans | Induction of EMT (V1 isoform) | Activation:
|
Inhibition of EMT (V2 isoform) | Inhibition:
| ||
Induction of stemness | Activation:
| ||
BGN | Extracellular/SLRPs | Induction of EMT | Cooperate with TGFβ/Snail—TNFα/NF-κB pathways |
Induction of stemness | Activation:
| ||
DEC | Extracellular/SLRPs | Inhibition of EMT | Inhibition:
|
ASPN | Extracellular/SLRPs | Induction of EMT | Activation:
|
LUM | Extracellular/SLRPs | Inhibition of EMT | Inhibition:
|
SPOCK1 | Extracellular/SPOCK | Induction of EMT | Activation:
|
AGRN | Pericellular | Induction of EMT | Activation:
|
COL XVIII/ENDOSTATIN | Pericellular | Inhibition of EMT | Inhibition:
|
SDC1 | Cell membrane/Syndecans | Induction of stemness | Regulation:
|
Inhibition of EMT | Inhibition:
| ||
SDC2 | Cell membrane/Syndecans | Induction of EMT | Activation:
|
SDC3 | Cell membrane/Syndecans | Induction of EMT | Activation:
|
SDC4 | Cell membrane/Syndecans | Induction of EMT | Activation:
|
BETAGLYCAN/ TGFBR3 | Cell membrane | Inhibition of EMT | Inhibition:
|
GPC1 | Cell membrane/Glypicans | Induction of EMT | Activation:
|
GPC3 | Cell membrane/Glypicans | Inhibition of EMT (Breast cancer) | Inhibition:
|
Induction of EMT (HCC) | Activation:
| ||
GPC4 | Cell membrane/Glypicans | Induction of stemness | Activation:
|
GPC5 | Cell membrane/Glypicans | Inhibition of EMT | Inhibition:
|
SRGN | Intracellular (Matrix secreted molecule) | Induction of EMT/stemness | Activation:
|
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Karagiorgou, Z.; Fountas, P.N.; Manou, D.; Knutsen, E.; Theocharis, A.D. Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness. Cancers 2022, 14, 5328. https://doi.org/10.3390/cancers14215328
Karagiorgou Z, Fountas PN, Manou D, Knutsen E, Theocharis AD. Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness. Cancers. 2022; 14(21):5328. https://doi.org/10.3390/cancers14215328
Chicago/Turabian StyleKaragiorgou, Zoi, Panagiotis N. Fountas, Dimitra Manou, Erik Knutsen, and Achilleas D. Theocharis. 2022. "Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness" Cancers 14, no. 21: 5328. https://doi.org/10.3390/cancers14215328
APA StyleKaragiorgou, Z., Fountas, P. N., Manou, D., Knutsen, E., & Theocharis, A. D. (2022). Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness. Cancers, 14(21), 5328. https://doi.org/10.3390/cancers14215328