Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy
Abstract
:1. Introduction
2. SHP-1/p-STAT3 Pathway in Cancers
3. SHP-1/STAT3 Pathway Is a Target in the Treatment of Human Malignancies
4. Selective Targeting SHP-1 Is Augmented by Combination Therapy with Chemotherapeutic Agents for STAT3 Signaling Blockade
5. Clinical Relevance of SHP-1/p-STAT3 in Cancers
6. Conclusions and Perspectives
Author Contributions
Conflicts of Interest
References
- Lim, C.P.; Cao, X. Structure, function, and regulation of STAT proteins. Mol. Biosyst. 2006, 2, 536–550. [Google Scholar] [CrossRef] [PubMed]
- Schindler, C.; Levy, D.E.; Decker, T. JAK-STAT signaling: From interferons to cytokines. J. Biol. Chem. 2007, 282, 20059–20063. [Google Scholar] [CrossRef] [PubMed]
- Santoni, M.; Massari, F.; Del Re, M.; Ciccarese, C.; Piva, F.; Principato, G.; Montironi, R.; Santini, D.; Danesi, R.; Tortora, G.; et al. Investigational therapies targeting signal transducer and activator of transcription 3 for the treatment of cancer. Expert Opin. Investig. Drugs 2015, 24, 809–824. [Google Scholar] [CrossRef] [PubMed]
- Subramaniam, A.; Shanmugam, M.K.; Perumal, E.; Li, F.; Nachiyappan, A.; Dai, X.; Swamy, S.N.; Ahn, K.S.; Kumar, A.P.; Tan, B.K.; et al. Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim. Biophys. Acta 2013, 1835, 46–60. [Google Scholar] [CrossRef] [PubMed]
- Bendell, J.C.; Hong, D.S.; Burris, H.A., 3rd; Naing, A.; Jones, S.F.; Falchook, G.; Bricmont, P.; Elekes, A.; Rock, E.P.; Kurzrock, R. Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors. Cancer Chemother. Pharmacol. 2014, 74, 125–130. [Google Scholar] [CrossRef] [PubMed]
- Hong, D.; Kurzrock, R.; Kim, Y.; Woessner, R.; Younes, A.; Nemunaitis, J.; Fowler, N.; Zhou, T.; Schmidt, J.; Jo, M.; et al. AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci. Transl. Med. 2015, 7, 314ra185. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Yue, P.; Page, B.D.; Li, T.; Zhao, W.; Namanja, A.T.; Paladino, D.; Zhao, J.; Chen, Y.; Gunning, P.T.; et al. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc. Natl. Acad. Sci. USA 2012, 109, 9623–9628. [Google Scholar] [CrossRef] [PubMed]
- Geiger, J.L.; Grandis, J.R.; Bauman, J.E. The STAT3 pathway as a therapeutic target in head and neck cancer: Barriers and innovations. Oral Oncol. 2016, 56, 84–92. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Crowe, P.J.; Goldstein, D.; Yang, J.L. STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (review). Int. J. Oncol. 2012, 41, 1181–1191. [Google Scholar] [PubMed]
- Furtek, S.L.; Backos, D.S.; Matheson, C.J.; Reigan, P. Strategies and Approaches of Targeting STAT3 for Cancer Treatment. ACS Chem. Biol. 2016, 11, 308–318. [Google Scholar] [CrossRef] [PubMed]
- Siveen, K.S.; Sikka, S.; Surana, R.; Dai, X.; Zhang, J.; Kumar, A.P.; Tan, B.K.; Sethi, G.; Bishayee, A. Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors. Biochim. Biophys. Acta 2014, 1845, 136–154. [Google Scholar] [CrossRef] [PubMed]
- Zhao, M.; Jiang, B.; Gao, F.H. Small molecule inhibitors of STAT3 for cancer therapy. Curr. Med. Chem. 2011, 18, 4012–4018. [Google Scholar] [CrossRef] [PubMed]
- Masciocchi, D.; Gelain, A.; Villa, S.; Meneghetti, F.; Barlocco, D. Signal transducer and activator of transcription 3 (STAT3): A promising target for anticancer therapy. Future Med. Chem. 2011, 3, 567–597. [Google Scholar] [CrossRef] [PubMed]
- Cafferkey, C.; Chau, I. Novel STAT 3 inhibitors for treating gastric cancer. Expert Opin. Investig. Drugs 2016, 25, 1023–1031. [Google Scholar] [CrossRef] [PubMed]
- Turkson, J.; Bowman, T.; Garcia, R.; Caldenhoven, E.; De Groot, R.P.; Jove, R. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol. Cell. Biol. 1998, 18, 2545–2552. [Google Scholar] [CrossRef] [PubMed]
- Niu, G.; Bowman, T.; Huang, M.; Shivers, S.; Reintgen, D.; Daud, A.; Chang, A.; Kraker, A.; Jove, R.; Yu, H. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene 2002, 21, 7001–7010. [Google Scholar] [CrossRef] [PubMed]
- Den Hertog, J.; Ostman, A.; Bohmer, F.D. Protein tyrosine phosphatases: Regulatory mechanisms. FEBS J. 2008, 275, 831–847. [Google Scholar] [CrossRef] [PubMed]
- Yamada, S.; Shiono, S.; Joo, A.; Yoshimura, A. Control mechanism of JAK/STAT signal transduction pathway. FEBS Lett. 2003, 534, 190–196. [Google Scholar] [CrossRef]
- Tai, W.T.; Cheng, A.L.; Shiau, C.W.; Huang, H.P.; Huang, J.W.; Chen, P.J.; Chen, K.F. Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma. J. Hepatol. 2011, 55, 1041–1048. [Google Scholar] [CrossRef] [PubMed]
- Beldi-Ferchiou, A.; Skouri, N.; Ben Ali, C.; Safra, I.; Abdelkefi, A.; Ladeb, S.; Mrad, K.; Ben Othman, T.; Ben Ahmed, M. Abnormal repression of SHP-1, SHP-2 and SOCS-1 transcription sustains the activation of the JAK/STAT3 pathway and the progression of the disease in multiple myeloma. PLoS ONE 2017, 12, e0174835. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.C.; Shiau, C.W.; Tai, W.T.; Hung, M.H.; Chu, P.Y.; Hsieh, F.S.; Lin, H.; Yu, H.C.; Chen, K.F. SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma. Oncogene 2015, 34, 5252–5263. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.Y.; Su, J.C.; Ni, M.H.; Tseng, L.M.; Chu, P.Y.; Wang, D.S.; Tai, W.T.; Kao, Y.P.; Hung, M.H.; Shiau, C.W.; et al. Obatoclax analog SC-2001 inhibits STAT3 phosphorylation through enhancing SHP-1 expression and induces apoptosis in human breast cancer cells. Breast Cancer Res. Treat. 2014, 146, 71–84. [Google Scholar] [CrossRef] [PubMed]
- Su, J.C.; Mar, A.C.; Wu, S.H.; Tai, W.T.; Chu, P.Y.; Wu, C.Y.; Tseng, L.M.; Lee, T.C.; Chen, K.F.; Liu, C.Y.; et al. Disrupting VEGF-A paracrine and autocrine loops by targeting SHP-1 suppresses triple negative breast cancer metastasis. Sci. Rep. 2016, 6, 28888. [Google Scholar] [CrossRef] [PubMed]
- Aggarwal, B.B.; Sethi, G.; Ahn, K.S.; Sandur, S.K.; Pandey, M.K.; Kunnumakkara, A.B.; Sung, B.; Ichikawa, H. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: Modern target but ancient solution. Ann. N. Y. Acad. Sci. 2006, 1091, 151–169. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, M.; Kaestel, C.G.; Eriksen, K.W.; Woetmann, A.; Stokkedal, T.; Kaltoft, K.; Geisler, C.; Ropke, C.; Odum, N. Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells. Leukemia 1999, 13, 735–738. [Google Scholar] [CrossRef] [PubMed]
- Cao, X.; Tay, A.; Guy, G.R.; Tan, Y.H. Activation and association of Stat3 with Src in v-Src-transformed cell lines. Mol. Cell. Biol. 1996, 16, 1595–1603. [Google Scholar] [CrossRef] [PubMed]
- Bromberg, J.F.; Horvath, C.M.; Besser, D.; Lathem, W.W.; Darnell, J.E., Jr. Stat3 activation is required for cellular transformation by v-src. Mol. Cell. Biol. 1998, 18, 2553–2558. [Google Scholar] [CrossRef] [PubMed]
- Ostman, A.; Hellberg, C.; Bohmer, F.D. Protein-tyrosine phosphatases and cancer. Nat. Rev. Cancer 2006, 6, 307–320. [Google Scholar] [CrossRef] [PubMed]
- David, M.; Chen, H.E.; Goelz, S.; Larner, A.C.; Neel, B.G. Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway by the SH2 domain-containing tyrosine phosphatase SHPTP1. Mol. Cell. Biol. 1995, 15, 7050–7058. [Google Scholar] [CrossRef] [PubMed]
- Jiao, H.; Berrada, K.; Yang, W.; Tabrizi, M.; Platanias, L.C.; Yi, T. Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1. Mol. Cell. Biol. 1996, 16, 6985–6992. [Google Scholar] [CrossRef] [PubMed]
- Haque, S.J.; Harbor, P.; Tabrizi, M.; Yi, T.; Williams, B.R. Protein-tyrosine phosphatase Shp-1 is a negative regulator of IL-4- and IL-13-dependent signal transduction. J. Biol. Chem. 1998, 273, 33893–33896. [Google Scholar] [CrossRef] [PubMed]
- Migone, T.S.; Cacalano, N.A.; Taylor, N.; Yi, T.; Waldmann, T.A.; Johnston, J.A. Recruitment of SH2-containing protein tyrosine phosphatase SHP-1 to the interleukin 2 receptor; loss of SHP-1 expression in human T-lymphotropic virus type I-transformed T cells. Proc. Natl. Acad. Sci. USA 1998, 95, 3845–3850. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.; Liang, X.; Niu, T.; Meng, W.; Zhao, Z.; Zhou, G.W. Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1. J. Biol. Chem. 1998, 273, 28199–28207. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.; Liu, L.; He, D.; Song, X.; Liang, X.; Zhao, Z.J.; Zhou, G.W. Crystal structure of human protein-tyrosine phosphatase SHP-1. J. Biol. Chem. 2003, 278, 6516–6520. [Google Scholar] [CrossRef] [PubMed]
- Thangaraju, M.; Sharma, K.; Liu, D.; Shen, S.H.; Srikant, C.B. Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. Cancer Res. 1999, 59, 1649–1654. [Google Scholar] [PubMed]
- Lopez, F.; Esteve, J.P.; Buscail, L.; Delesque, N.; Saint-Laurent, N.; Theveniau, M.; Nahmias, C.; Vaysse, N.; Susini, C. The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. J. Biol. Chem. 1997, 272, 24448–24454. [Google Scholar] [CrossRef] [PubMed]
- Zapata, P.D.; Ropero, R.M.; Valencia, A.M.; Buscail, L.; Lopez, J.I.; Martin-Orozco, R.M.; Prieto, J.C.; Angulo, J.; Susini, C.; Lopez-Ruiz, P.; et al. Autocrine regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase (SHP)-1. J. Clin. Endocrinol. Metab. 2002, 87, 915–926. [Google Scholar] [CrossRef] [PubMed]
- Delibrias, C.C.; Floettmann, J.E.; Rowe, M.; Fearon, D.T. Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes. J. Exp. Med. 1997, 186, 1575–1583. [Google Scholar] [CrossRef] [PubMed]
- Wu, C.; Sun, M.; Liu, L.; Zhou, G.W. The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene 2003, 306, 1–12. [Google Scholar] [CrossRef]
- Chim, C.S.; Fung, T.K.; Cheung, W.C.; Liang, R.; Kwong, Y.L. SOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway. Blood 2004, 103, 4630–4635. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Wang, H.Y.; Marzec, M.; Raghunath, P.N.; Nagasawa, T.; Wasik, M.A. STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. Proc. Natl. Acad. Sci. USA 2005, 102, 6948–6953. [Google Scholar] [CrossRef] [PubMed]
- Shaulian, E.; Karin, M. AP-1 as a regulator of cell life and death. Nat. Cell Biol. 2002, 4, E131–E136. [Google Scholar] [CrossRef] [PubMed]
- Zugowski, C.; Lieder, F.; Muller, A.; Gasch, J.; Corvinus, F.M.; Moriggl, R.; Friedrich, K. STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter. Biol. Chem. 2011, 392, 449–459. [Google Scholar] [CrossRef] [PubMed]
- Du, Q.; Geller, D.A. Cross-Regulation Between Wnt and NF-kappaB Signaling Pathways. Forum Immunopathol. Dis. Ther. 2010, 1, 155–181. [Google Scholar] [CrossRef]
- Kawada, M.; Seno, H.; Uenoyama, Y.; Sawabu, T.; Kanda, N.; Fukui, H.; Shimahara, Y.; Chiba, T. Signal transducers and activators of transcription 3 activation is involved in nuclear accumulation of beta-catenin in colorectal cancer. Cancer Res. 2006, 66, 2913–2917. [Google Scholar] [CrossRef] [PubMed]
- Yan, S.; Zhou, C.; Zhang, W.; Zhang, G.; Zhao, X.; Yang, S.; Wang, Y.; Lu, N.; Zhu, H.; Xu, N. Beta-Catenin/TCF pathway upregulates STAT3 expression in human esophageal squamous cell carcinoma. Cancer Lett. 2008, 271, 85–97. [Google Scholar] [CrossRef] [PubMed]
- Fragoso, M.A.; Patel, A.K.; Nakamura, R.E.; Yi, H.; Surapaneni, K.; Hackam, A.S. The Wnt/beta-catenin pathway cross-talks with STAT3 signaling to regulate survival of retinal pigment epithelium cells. PLoS ONE 2012, 7, e46892. [Google Scholar] [CrossRef] [PubMed]
- Hao, J.; Li, T.G.; Qi, X.; Zhao, D.F.; Zhao, G.Q. WNT/beta-catenin pathway up-regulates Stat3 and converges on LIF to prevent differentiation of mouse embryonic stem cells. Dev. Biol. 2006, 290, 81–91. [Google Scholar] [CrossRef] [PubMed]
- Ye, S.; Zhang, D.; Cheng, F.; Wilson, D.; Mackay, J.; He, K.; Ban, Q.; Lv, F.; Huang, S.; Liu, D.; et al. Wnt/beta-catenin and LIF-Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal. J. Cell Sci. 2016, 129, 269–276. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Mao, R.; Yang, J. NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell 2013, 4, 176–185. [Google Scholar] [CrossRef] [PubMed]
- Grivennikov, S.I.; Karin, M. Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010, 21, 11–19. [Google Scholar] [CrossRef] [PubMed]
- Bollrath, J.; Greten, F.R. IKK/NF-kappaB and STAT3 pathways: Central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep. 2009, 10, 1314–1319. [Google Scholar] [CrossRef] [PubMed]
- Forget, G.; Siminovitch, K.A.; Brochu, S.; Rivest, S.; Radzioch, D.; Olivier, M. Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis. Eur. J. Immunol. 2001, 31, 3185–3196. [Google Scholar] [CrossRef]
- Forget, G.; Gregory, D.J.; Whitcombe, L.A.; Olivier, M. Role of host protein tyrosine phosphatase SHP-1 in Leishmania donovani-induced inhibition of nitric oxide production. Infect. Immun. 2006, 74, 6272–6279. [Google Scholar] [CrossRef] [PubMed]
- Massa, P.T.; Wu, C. Increased inducible activation of NF-κB and responsive genes in astrocytes deficient in the protein tyrosine phosphatase SHP-1. J. Interferon Cytokine Res. 1998, 18, 499–507. [Google Scholar] [CrossRef] [PubMed]
- Duchesne, C.; Charland, S.; Asselin, C.; Nahmias, C.; Rivard, N. Negative regulation of beta-catenin signaling by tyrosine phosphatase SHP-1 in intestinal epithelial cells. J. Biol. Chem. 2003, 278, 14274–14283. [Google Scholar] [CrossRef] [PubMed]
- Simpson, D.; Keating, G.M. Sorafenib: In hepatocellular carcinoma. Drugs 2008, 68, 251–258. [Google Scholar] [CrossRef] [PubMed]
- Yang, F.; Van Meter, T.E.; Buettner, R.; Hedvat, M.; Liang, W.; Kowolik, C.M.; Mepani, N.; Mirosevich, J.; Nam, S.; Chen, M.Y.; et al. Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas. Mol. Cancer Ther. 2008, 7, 3519–3526. [Google Scholar] [CrossRef] [PubMed]
- Huang, S.; Sinicrope, F.A. Sorafenib inhibits STAT3 activation to enhance TRAIL-mediated apoptosis in human pancreatic cancer cells. Mol. Cancer Ther. 2010, 9, 742–750. [Google Scholar] [CrossRef] [PubMed]
- Yang, F.; Brown, C.; Buettner, R.; Hedvat, M.; Starr, R.; Scuto, A.; Schroeder, A.; Jensen, M.; Jove, R. Sorafenib induces growth arrest and apoptosis of human glioblastoma cells through the dephosphorylation of signal transducers and activators of transcription 3. Mol. Cancer Ther. 2010, 9, 953–962. [Google Scholar] [CrossRef] [PubMed]
- Chai, H.; Luo, A.Z.; Weerasinghe, P.; Brown, R.E. Sorafenib downregulates ERK/Akt and STAT3 survival pathways and induces apoptosis in a human neuroblastoma cell line. Int. J. Clin. Exp. Pathol. 2010, 3, 408–415. [Google Scholar] [PubMed]
- Zhao, W.; Zhang, T.; Qu, B.; Wu, X.; Zhu, X.; Meng, F.; Gu, Y.; Shu, Y.; Shen, Y.; Sun, Y.; et al. Sorafenib induces apoptosis in HL60 cells by inhibiting Src kinase-mediated STAT3 phosphorylation. Anti Cancer Drugs 2011, 22, 79–88. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.F.; Tai, W.T.; Liu, T.H.; Huang, H.P.; Lin, Y.C.; Shiau, C.W.; Li, P.K.; Chen, P.J.; Cheng, A.L. Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3. Clin. Cancer Res. 2010, 16, 5189–5199. [Google Scholar] [CrossRef] [PubMed]
- Chao, T.I.; Tai, W.T.; Hung, M.H.; Tsai, M.H.; Chen, M.H.; Chang, M.J.; Shiau, C.W.; Chen, K.F. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy. Cancer Lett. 2016, 371, 205–213. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.F.; Tai, W.T.; Hsu, C.Y.; Huang, J.W.; Liu, C.Y.; Chen, P.J.; Kim, I.; Shiau, C.W. Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity. Eur. J. Med. Chem. 2012, 55, 220–227. [Google Scholar] [CrossRef] [PubMed]
- Adnane, L.; Trail, P.A.; Taylor, I.; Wilhelm, S.M. Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006, 407, 597–612. [Google Scholar] [PubMed]
- Liu, L.; Cao, Y.; Chen, C.; Zhang, X.; McNabola, A.; Wilkie, D.; Wilhelm, S.; Lynch, M.; Carter, C. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006, 66, 11851–11858. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.Y.; Tseng, L.M.; Su, J.C.; Chang, K.C.; Chu, P.Y.; Tai, W.T.; Shiau, C.W.; Chen, K.F. Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells. Breast Cancer Res. BCR 2013, 15, R63. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.Y.; Su, J.C.; Huang, T.T.; Chu, P.Y.; Huang, C.T.; Wang, W.L.; Lee, C.H.; Lau, K.Y.; Tsai, W.C.; Yang, H.P.; et al. Sorafenib analogue SC-60 induces apoptosis through the SHP-1/STAT3 pathway and enhances docetaxel cytotoxicity in triple-negative breast cancer cells. Mol. Oncol. 2017, 11, 266–279. [Google Scholar] [CrossRef] [PubMed]
- Tai, W.T.; Shiau, C.W.; Chen, P.J.; Chu, P.Y.; Huang, H.P.; Liu, C.Y.; Huang, J.W.; Chen, K.F. Discovery of novel Src homology region 2 domain-containing phosphatase 1 agonists from sorafenib for the treatment of hepatocellular carcinoma. Hepatology 2014, 59, 190–201. [Google Scholar] [CrossRef] [PubMed]
- Hu, M.H.; Chen, L.J.; Chen, Y.L.; Tsai, M.S.; Shiau, C.W.; Chao, T.I.; Liu, C.Y.; Kao, J.H.; Chen, K.F. Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the treatment of cholangiocarcinoma. Oncotarget 2017. [Google Scholar] [CrossRef] [PubMed]
- Tai, W.T.; Shiau, C.W.; Li, Y.S.; Chen, Y.L.; Chu, P.Y.; Huang, J.W.; Hsu, C.Y.; Hsu, Y.C.; Chen, P.J.; Chen, K.F. SC-60, a dimer-based sorafenib derivative, shows a better anti-hepatocellular carcinoma effect than sorafenib in a preclinical hepatocellular carcinoma model. Mol. Cancer Ther. 2014, 13, 27–36. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.C.; Teng, H.W.; Shiau, C.W.; Tai, W.T.; Hung, M.H.; Yang, S.H.; Jiang, J.K.; Chen, K.F. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer. Neoplasia 2015, 17, 687–696. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.C.; Teng, H.W.; Shiau, C.W.; Lin, H.; Hung, M.H.; Chen, Y.L.; Huang, J.W.; Tai, W.T.; Yu, H.C.; Chen, K.F. SHP-1 is a target of regorafenib in colorectal cancer. Oncotarget 2014, 5, 6243–6251. [Google Scholar] [CrossRef] [PubMed]
- Tai, W.T.; Chu, P.Y.; Shiau, C.W.; Chen, Y.L.; Li, Y.S.; Hung, M.H.; Chen, L.J.; Chen, P.L.; Su, J.C.; Lin, P.Y.; et al. STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma. Clin. Cancer Res. 2014, 20, 5768–5776. [Google Scholar] [CrossRef] [PubMed]
- Tai, W.T.; Cheng, A.L.; Shiau, C.W.; Liu, C.Y.; Ko, C.H.; Lin, M.W.; Chen, P.J.; Chen, K.F. Dovitinib induces apoptosis and overcomes sorafenib resistance in hepatocellular carcinoma through SHP-1-mediated inhibition of STAT3. Mol. Cancer Ther. 2012, 11, 452–463. [Google Scholar] [CrossRef] [PubMed]
- Tai, W.T.; Shiau, C.W.; Li, Y.S.; Chang, C.W.; Huang, J.W.; Hsueh, T.T.; Yu, H.C.; Chen, K.F. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. J. Hepatol. 2014, 61, 89–97. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Chiang, S.Y.; Nam, D.; Chung, W.S.; Lee, J.; Na, Y.S.; Sethi, G.; Ahn, K.S. Capillarisin inhibits constitutive and inducible STAT3 activation through induction of SHP-1 and SHP-2 tyrosine phosphatases. Cancer Lett. 2014, 345, 140–148. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.H.; Ahn, K.S.; Jeong, S.J.; Kwon, T.R.; Jung, J.H.; Yun, S.M.; Han, I.; Lee, S.G.; Kim, D.K.; Kang, M.; et al. Janus activated kinase 2/signal transducer and activator of transcription 3 pathway mediates icariside II-induced apoptosis in U266 multiple myeloma cells. Eur. J. Pharmacol. 2011, 654, 10–16. [Google Scholar] [CrossRef] [PubMed]
- Pandey, M.K.; Sung, B.; Aggarwal, B.B. Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP-1 in human multiple myeloma cells. Int. J. Cancer 2010, 127, 282–292. [Google Scholar] [CrossRef] [PubMed]
- Rhee, Y.H.; Jeong, S.J.; Lee, H.J.; Lee, H.J.; Koh, W.; Jung, J.H.; Kim, S.H.; Sung-Hoon, K. Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells. BMC Cancer 2012, 12, 28. [Google Scholar] [CrossRef] [PubMed]
- Jung, J.H.; Yun, M.; Choo, E.J.; Kim, S.H.; Jeong, M.S.; Jung, D.B.; Lee, H.; Kim, E.O.; Kato, N.; Kim, B.; et al. A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia. Br. J. Pharmacol. 2015, 172, 3565–3578. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.C.; Ahn, K.S.; Jeong, S.J.; Jung, J.H.; Kwon, T.R.; Rhee, Y.H.; Kim, S.H.; Kim, S.Y.; Yoon, H.J.; Zhu, S.; et al. Signal transducer and activator of transcription 3 pathway mediates genipin-induced apoptosis in U266 multiple myeloma cells. J. Cell. Biochem. 2011, 112, 1552–1562. [Google Scholar] [CrossRef] [PubMed]
- Kunnumakkara, A.B.; Nair, A.S.; Sung, B.; Pandey, M.K.; Aggarwal, B.B. Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1. Mol. Cancer Res. MCR 2009, 7, 118–128. [Google Scholar] [CrossRef] [PubMed]
- Baek, S.H.; Lee, J.H.; Kim, C.; Ko, J.H.; Ryu, S.H.; Lee, S.G.; Yang, W.M.; Um, J.Y.; Chinnathambi, A.; Alharbi, S.A.; et al. Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase. Molecules 2017. [Google Scholar] [CrossRef] [PubMed]
- Subramaniam, A.; Shanmugam, M.K.; Ong, T.H.; Li, F.; Perumal, E.; Chen, L.; Vali, S.; Abbasi, T.; Kapoor, S.; Ahn, K.S.; et al. Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3. Br. J. Pharmacol. 2013, 170, 807–821. [Google Scholar] [CrossRef] [PubMed]
- Rajendran, P.; Li, F.; Manu, K.A.; Shanmugam, M.K.; Loo, S.Y.; Kumar, A.P.; Sethi, G. gamma-Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: Potential role as an antiproliferative, pro-apoptotic and chemosensitizing agent. Br. J. Pharmacol. 2011, 163, 283–298. [Google Scholar] [CrossRef] [PubMed]
- Rajendran, P.; Li, F.; Shanmugam, M.K.; Vali, S.; Abbasi, T.; Kapoor, S.; Ahn, K.S.; Kumar, A.P.; Sethi, G. Honokiol inhibits signal transducer and activator of transcription-3 signaling, proliferation, and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J. Cell. Physiol. 2012, 227, 2184–2195. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Li, S.; Li, J.; Yin, F.; Hua, Y.; Wang, Z.; Lin, B.; Wang, H.; Zou, D.; Zhou, Z.; et al. Natural product pectolinarigenin inhibits osteosarcoma growth and metastasis via SHP-1-mediated STAT3 signaling inhibition. Cell Death Dis. 2016, 7, e2421. [Google Scholar] [CrossRef] [PubMed]
- Shanmugam, M.K.; Rajendran, P.; Li, F.; Kim, C.; Sikka, S.; Siveen, K.S.; Kumar, A.P.; Ahn, K.S.; Sethi, G. Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model. Mol. Carcinogenes. 2015, 54, 971–985. [Google Scholar] [CrossRef] [PubMed]
- Song, S.; Su, Z.; Xu, H.; Niu, M.; Chen, X.; Min, H.; Zhang, B.; Sun, G.; Xie, S.; Wang, H.; et al. Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1. Cell Death Dis. 2017, 8, e2612. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.F.; Chen, H.L.; Shiau, C.W.; Liu, C.Y.; Chu, P.Y.; Tai, W.T.; Ichikawa, K.; Chen, P.J.; Cheng, A.L. Sorafenib and its derivative SC-49 sensitize hepatocellular carcinoma cells to CS-1008, a humanized anti-TNFRSF10B (DR5) antibody. Br. J. Pharmacol. 2013, 168, 658–672. [Google Scholar] [CrossRef] [PubMed]
- Huang, C.Y.; Tai, W.T.; Hsieh, C.Y.; Hsu, W.M.; Lai, Y.J.; Chen, L.J.; Shiau, C.W.; Chen, K.F. A sorafenib derivative and novel SHP-1 agonist, SC-59, acts synergistically with radiotherapy in hepatocellular carcinoma cells through inhibition of STAT3. Cancer Lett. 2014, 349, 136–143. [Google Scholar] [CrossRef] [PubMed]
- Su, J.C.; Chiang, H.C.; Tseng, P.H.; Tai, W.T.; Hsu, C.Y.; Li, Y.S.; Huang, J.W.; Ko, C.H.; Lin, M.W.; Chu, P.Y.; et al. RFX-1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells. Carcinogenesis 2014, 35, 2807–2814. [Google Scholar] [CrossRef] [PubMed]
- Su, J.C.; Tseng, P.H.; Wu, S.H.; Hsu, C.Y.; Tai, W.T.; Li, Y.S.; Chen, I.T.; Liu, C.Y.; Chen, K.F.; Shiau, C.W. SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma. Neoplasia 2014, 16, 595–605. [Google Scholar] [CrossRef] [PubMed]
- Olweny, C.L.; Toya, T.; Katongole-Mbidde, E.; Mugerwa, J.; Kyalwazi, S.K.; Cohen, H. Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication. Cancer 1975, 36, 1250–1257. [Google Scholar] [CrossRef]
- Stalmeier, P.F.; van Tol-Geerdink, J.J.; van Lin, E.N.; Schimmel, E.; Huizenga, H.; van Daal, W.A.; Leer, J.W. Doctors’ and patients’ preferences for participation and treatment in curative prostate cancer radiotherapy. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2007, 25, 3096–3100. [Google Scholar] [CrossRef] [PubMed]
- Yeo, W.; Mok, T.S.; Zee, B.; Leung, T.W.; Lai, P.B.; Lau, W.Y.; Koh, J.; Mo, F.K.; Yu, S.C.; Chan, A.T.; et al. A randomized phase III study of doxorubicin versus cisplatin/interferon α-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J. Natl. Cancer Inst. 2005, 97, 1532–1538. [Google Scholar] [CrossRef] [PubMed]
- Choi, T.K.; Lee, N.W.; Wong, J. Chemotherapy for advanced hepatocellular carcinoma. Adriamycin versus quadruple chemotherapy. Cancer 1984, 53, 401–405. [Google Scholar] [CrossRef]
- Melia, W.M.; Johnson, P.J.; Williams, R. Induction of remission in hepatocellular carcinoma. A comparison of VP 16 with adriamycin. Cancer 1983, 51, 206–210. [Google Scholar] [CrossRef]
- Falkson, G.; Moertel, C.G.; Lavin, P.; Pretorius, F.J.; Carbone, P.P. Chemotherapy studies in primary liver cancer: A prospective randomized clinical trial. Cancer 1978, 42, 2149–2156. [Google Scholar] [CrossRef]
- Bachawal, S.V.; Wali, V.B.; Sylvester, P.W. Combined gamma-tocotrienol and erlotinib/gefitinib treatment suppresses Stat and Akt signaling in murine mammary tumor cells. Anticancer Res. 2010, 30, 429–437. [Google Scholar] [PubMed]
- Huang, C.Y.; Tai, W.T.; Wu, S.Y.; Shih, C.T.; Chen, M.H.; Tsai, M.H.; Kuo, C.W.; Shiau, C.W.; Hung, M.H.; Chen, K.F. Dovitinib Acts As a Novel Radiosensitizer in Hepatocellular Carcinoma by Targeting SHP-1/STAT3 Signaling. Int. J. Radiat. Oncol. Biol. Phys. 2016, 95, 761–771. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.F.; Chen, H.L.; Liu, C.Y.; Tai, W.T.; Ichikawa, K.; Chen, P.J.; Cheng, A.L. Dovitinib sensitizes hepatocellular carcinoma cells to TRAIL and tigatuzumab, a novel anti-DR5 antibody, through SHP-1-dependent inhibition of STAT3. Biochem. Pharmacol. 2012, 83, 769–777. [Google Scholar] [CrossRef] [PubMed]
- Al-Jamal, H.A.; Mat Jusoh, S.A.; Hassan, R.; Johan, M.F. Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia. BMC Cancer 2015, 15, 869. [Google Scholar] [CrossRef] [PubMed]
- Kong, J.; Kong, F.; Gao, J.; Zhang, Q.; Dong, S.; Gu, F.; Ke, S.; Pan, B.; Shen, Q.; Sun, H.; et al. YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma. Mol. Cancer 2014, 13, 7. [Google Scholar] [CrossRef] [PubMed]
- Sandur, S.K.; Pandey, M.K.; Sung, B.; Aggarwal, B.B. 5-hydroxy-2-methyl-1,4-naphthoquinone, a vitamin K3 analogue, suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase, SHP-1: Potential role in chemosensitization. Mol. Cancer Res. MCR 2010, 8, 107–118. [Google Scholar] [CrossRef] [PubMed]
- Thomas, S.J.; Snowden, J.A.; Zeidler, M.P.; Danson, S.J. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br. J. Cancer 2015, 113, 365–371. [Google Scholar] [CrossRef] [PubMed]
- Chai, E.Z.; Shanmugam, M.K.; Arfuso, F.; Dharmarajan, A.; Wang, C.; Kumar, A.P.; Samy, R.P.; Lim, L.H.; Wang, L.; Goh, B.C.; et al. Targeting transcription factor STAT3 for cancer prevention and therapy. Pharmacol. Ther. 2016, 162, 86–97. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.R.; Seo, H.S.; Choi, H.S.; Cho, S.G.; Kim, Y.K.; Hong, E.H.; Shin, Y.C.; Ko, S.G. Trichosanthes kirilowii Ethanol Extract and Cucurbitacin D Inhibit Cell Growth and Induce Apoptosis through Inhibition of STAT3 Activity in Breast Cancer Cells. Evid. Based Complement. Altern. Med. 2013, 2013, 975350. [Google Scholar] [CrossRef] [PubMed]
- Walker, S.R.; Xiang, M.; Frank, D.A. Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer. Mol. Cell. Endocrinol. 2014, 382, 616–621. [Google Scholar] [CrossRef] [PubMed]
- Garcia, R.; Bowman, T.L.; Niu, G.; Yu, H.; Minton, S.; Muro-Cacho, C.A.; Cox, C.E.; Falcone, R.; Fairclough, R.; Parsons, S.; et al. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 2001, 20, 2499–2513. [Google Scholar] [CrossRef] [PubMed]
- Sharma, Y.; Bashir, S.; Bhardwaj, P.; Ahmad, A.; Khan, F. Protein tyrosine phosphatase SHP-1: Resurgence as new drug target for human autoimmune disorders. Immunol. Res. 2016, 64, 804–819. [Google Scholar] [CrossRef] [PubMed]
- Paling, N.R.; Welham, M.J. Tyrosine phosphatase SHP-1 acts at different stages of development to regulate hematopoiesis. Blood 2005, 105, 4290–4297. [Google Scholar] [CrossRef] [PubMed]
- Tassidis, H.; Brokken, L.J.; Jirstrom, K.; Ehrnstrom, R.; Ponten, F.; Ulmert, D.; Bjartell, A.; Harkonen, P.; Wingren, A.G. Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer. Int. J. Cancer 2010, 126, 2296–2307. [Google Scholar] [CrossRef] [PubMed]
- Insabato, L.; Amelio, I.; Quarto, M.; Zannetti, A.; Tolino, F.; de Mauro, G.; Cerchia, L.; Riccio, P.; Baumhoer, D.; Condorelli, G.; et al. Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors. Oncology 2009, 77, 378–384. [Google Scholar] [CrossRef] [PubMed]
- Peng, G.; Cao, R.; Xue, J.; Li, P.; Zou, Z.; Huang, J.; Ding, Q. Increased expression of SHP-1 is associated with local recurrence after radiotherapy in patients with nasopharyngeal carcinoma. Radiol. Oncol. 2014, 48, 40–49. [Google Scholar] [CrossRef] [PubMed]
- Tao, X.H.; Shen, J.G.; Pan, W.L.; Dong, Y.E.; Meng, Q.; Honn, K.V.; Jin, R. Significance of SHP-1 and SHP-2 expression in human papillomavirus infected Condyloma acuminatum and cervical cancer. Pathol. Oncol. Res. POR 2008, 14, 365–371. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.C.; Teng, H.W.; Shiau, C.W.; Tai, W.T.; Hung, M.H.; Yang, S.H.; Jiang, J.K.; Chen, K.F. Regorafenib (Stivarga) pharmacologically targets epithelial-mesenchymal transition in colorectal cancer. Oncotarget 2016, 7, 64136–64147. [Google Scholar] [CrossRef] [PubMed]
- Aschauer, L.; Muller, P.A. Novel targets and interaction partners of mutant p53 Gain-Of-Function. Biochem. Soc. Trans. 2016, 44, 460–466. [Google Scholar] [CrossRef] [PubMed]
- Watson, H.A.; Wehenkel, S.; Matthews, J.; Ager, A. SHP-1: The next checkpoint target for cancer immunotherapy? Biochem. Soc. Trans. 2016, 44, 356–362. [Google Scholar] [CrossRef] [PubMed]
- Iype, T.; Sankarshanan, M.; Mauldin, I.S.; Mullins, D.W.; Lorenz, U. The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. J. Immunol. 2010, 185, 6115–6127. [Google Scholar] [CrossRef] [PubMed]
- Sathish, J.G.; Dolton, G.; Leroy, F.G.; Matthews, R.J. Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1 increases CD8+ T cell-APC conjugate formation and is associated with enhanced in vivo CTL function. J. Immunol. 2007, 178, 330–337. [Google Scholar] [CrossRef] [PubMed]
© 2017 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 (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Huang, T.-T.; Su, J.-C.; Liu, C.-Y.; Shiau, C.-W.; Chen, K.-F. Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy. Int. J. Mol. Sci. 2017, 18, 1234. https://doi.org/10.3390/ijms18061234
Huang T-T, Su J-C, Liu C-Y, Shiau C-W, Chen K-F. Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy. International Journal of Molecular Sciences. 2017; 18(6):1234. https://doi.org/10.3390/ijms18061234
Chicago/Turabian StyleHuang, Tzu-Ting, Jung-Chen Su, Chun-Yu Liu, Chung-Wai Shiau, and Kuen-Feng Chen. 2017. "Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy" International Journal of Molecular Sciences 18, no. 6: 1234. https://doi.org/10.3390/ijms18061234