Protein Tyrosine Phosphatase 1B (PTP1B): Insights into its New Implications
in Tumorigenesis

Pei-Jie      Chen; Yun-Tian      Zhang
Abstract

In vivo, tyrosine phosphorylation is a reversible and dynamic process governed by the opposing activities of protein tyrosine kinases and phosphatases. Defective or inappropriate operation of these proteins leads to aberrant tyrosine phosphorylation, which contributes to the development of many human diseases, including cancers. PTP1B, a non-transmembrane phosphatase, is generally considered a negative regulator of the metabolic signaling pathways and a promising drug target for type II diabetes and obesity. Recently, PTP1B is gaining considerable interest due to its important function and therapeutic potential in other diseases. An increasing number of studies have indicated that PTP1B plays a vital role in the initiation and progression of cancers and could be a target for new cancer therapies. Following recent advances in the aspects mentioned above, this review is focused on the major functions of PTP1B in different types of cancer and the underlying mechanisms behind these functions, as well as the potential pharmacological effects of PTP1B inhibitors in cancer therapy.
Keywords: Protein Tyrosine Phosphatase (PTP), Protein Tyrosine Phosphatase 1B (PTP1B), cancer, tumor promoter, tumor suppressor, tyrosine phosphorylation.
Graphical Abstract

[1] 
Monteiro, H.P.; Arai, R.J.; Travassos, L.R. Protein tyrosine phosphorylation and protein tyrosine nitration in redox signaling. Antioxid. Redox Signal.,  2008, 10(5), 843-889.
[http://dx.doi.org/10.1089/ars.2007.1853] [PMID:  18220476] 
[2] 
Lim, W.A.; Pawson, T. Phosphotyrosine signaling: Evolving a new cellular communication system. Cell,  2010, 142(5), 661-667.
[http://dx.doi.org/10.1016/j.cell.2010.08.023] [PMID:  20813250] 
[3] 
Sun, H.; Tonks, N.K. The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem. Sci.,  1994, 19(11), 480-485.
[http://dx.doi.org/10.1016/0968-0004(94)90134-1] [PMID:  7855891] 
[4] 
Frankson, R.; Yu, Z.H.; Bai, Y.; Li, Q.; Zhang, R.Y.; Zhang, Z.Y. Therapeutic targeting of oncogenic tyrosine phosphatases. Cancer Res.,  2017, 77(21), 5701-5705.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-1510] [PMID:  28855209] 
[5] 
Gurzov, E.N.; Stanley, W.J.; Brodnicki, T.C.; Thomas, H.E. Protein tyrosine phosphatases: Molecular switches in metabolism and diabetes. Trends Endocrinol. Metab.,  2015, 26(1), 30-39.
[http://dx.doi.org/10.1016/j.tem.2014.10.004] [PMID:  25432462] 
[6] 
Loilome, W.; Dokduang, H. Protein kinases as targets for opisthorchis viverrini- associated cholangiocarcinoma therapy. Curr. Pharm. Des.,  2017, 23(29), 4281-4289.
[http://dx.doi.org/10.2174/1381612823666170710145019] [PMID:  28699535] 
[7] 
Wu, P.; Nielsen, T.E.; Clausen, M.H. Small-molecule kinase inhibitors: An analysis of FDA-approved drugs. Drug Discov. Today,  2016, 21(1), 5-10.
[http://dx.doi.org/10.1016/j.drudis.2015.07.008] [PMID:  26210956] 
[8] 
Liu, F.T.; Li, N.G.; Zhang, Y.M.; Xie, W.C.; Yang, S.P.; Lu, T.; Shi, Z.H. Recent advance in the development of novel, selective and potent FGFR inhibitors. Eur. J. Med. Chem.,  2020, 186, 111884.
[http://dx.doi.org/10.1016/j.ejmech.2019.111884] [PMID:  31761386] 
[9] 
Speir, M.; Nowell, C.J.; Chen, A.A.; O’Donnell, J.A.; Shamie, I.S.; Lakin, P.R.; D’Cruz, A.A.; Braun, R.O.; Babon, J.J.; Lewis, R.S.; Bliss-Moreau, M.; Shlomovitz, I.; Wang, S.; Cengia, L.H.; Stoica, A.I.; Hakem, R.; Kelliher, M.A.; O’Reilly, L.A.; Patsiouras, H.; Lawlor, K.E.; Weller, E.; Lewis, N.E.; Roberts, A.W.; Gerlic, M.; Croker, B.A. Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation. Nat. Immunol.,  2020, 21(1), 54-64.
[http://dx.doi.org/10.1038/s41590-019-0550-7] [PMID:  31819256] 
[10] 
Abdollahi, P.; Kohn, M.; Borset, M. Protein tyrosine phosphatases in multiple myeloma. Cancer Lett.,  2021, 501, 105-113.
[PMID:  33290866] 
[11] 
Tonks, N.K.; Diltz, C.D.; Fischer, E.H. Purification of the major protein-tyrosine-phosphatases of human placenta. J. Biol. Chem.,  1988, 263(14), 6722-6730.
[http://dx.doi.org/10.1016/S0021-9258(18)68702-2] [PMID:  2834386] 
[12] 
Ukkola, O.; Santaniemi, M. Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co-morbidities. J. Intern. Med.,  2002, 251(6), 467-475.
[http://dx.doi.org/10.1046/j.1365-2796.2002.00992.x] [PMID:  12028501] 
[13] 
Johnson, T.O.; Ermolieff, J.; Jirousek, M.R. Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat. Rev. Drug Discov.,  2002, 1(9), 696-709.
[http://dx.doi.org/10.1038/nrd895] [PMID:  12209150] 
[14] 
Liu, H.; Wu, Y.; Zhu, S.; Liang, W.; Wang, Z.; Wang, Y.; Lv, T.; Yao, Y.; Yuan, D.; Song, Y. PTP1B promotes cell proliferation and metastasis through activating Src and ERK1/2 in non-small cell lung cancer. Cancer Lett.,  2015, 359(2), 218-225.
[http://dx.doi.org/10.1016/j.canlet.2015.01.020] [PMID:  25617799] 
[15] 
Wang, J.; Chen, X.; Liu, B.; Zhu, Z. Suppression of PTP1B in gastric cancer cells in vitro induces a change in the genome-wide expression profile and inhibits gastric cancer cell growth. Cell Biol. Int.,  2010, 34(7), 747-753.
[http://dx.doi.org/10.1042/CBI20090447] [PMID:  20388125] 
[16] 
Suwaki, N.; Vanhecke, E.; Atkins, K.M.; Graf, M.; Swabey, K.; Huang, P.; Schraml, P.; Moch, H.; Cassidy, A.M.; Brewer, D.; Al-Lazikani, B.; Workman, P.; De-Bono, J.; Kaye, S.B.; Larkin, J.; Gore, M.E.; Sawyers, C.L.; Nelson, P.; Beer, T.M.; Geng, H.; Gao, L.; Qian, D.Z.; Alumkal, J.J.; Thomas, G.; Thomas, G.V. A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma. Sci. Transl. Med.,  2011, 3(85), 85ra47.
[http://dx.doi.org/10.1126/scitranslmed.3002004] [PMID:  21632985] 
[17] 
Tonks, N.K. Protein tyrosine phosphatases: From genes, to function, to disease. Nat. Rev. Mol. Cell Biol.,  2006, 7(11), 833-846.
[http://dx.doi.org/10.1038/nrm2039] [PMID:  17057753] 
[18] 
Brown-Shimer, S.; Johnson, K.A.; Lawrence, J.B.; Johnson, C.; Bruskin, A.; Green, N.R.; Hill, D.E. Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B. Proc. Natl. Acad. Sci. USA,  1990, 87(13), 5148-5152.
[http://dx.doi.org/10.1073/pnas.87.13.5148] [PMID:  2164224] 
[19] 
Anderie, I.; Schulz, I.; Schmid, A. Characterization of the C-terminal ER membrane anchor of PTP1B. Exp. Cell Res.,  2007, 313(15), 3189-3197.
[http://dx.doi.org/10.1016/j.yexcr.2007.05.025] [PMID:  17643420] 
[20] 
Frangioni, J.V.; Beahm, P.H.; Shifrin, V.; Jost, C.A.; Neel, B.G. The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell,  1992, 68(3), 545-560.
[http://dx.doi.org/10.1016/0092-8674(92)90190-N] [PMID:  1739967] 
[21] 
Liu, F.; Hill, D.E.; Chernoff, J. Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas). J. Biol. Chem.,  1996, 271(49), 31290-31295.
[http://dx.doi.org/10.1074/jbc.271.49.31290] [PMID:  8940134] 
[22] 
Siegel, R.; Ma, J.; Zou, Z.; Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin.,  2014, 64(1), 9-29.
[http://dx.doi.org/10.3322/caac.21208] [PMID:  24399786] 
[23] 
Molina, J.R.; Yang, P.; Cassivi, S.D.; Schild, S.E.; Adjei, A.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin. Proc.,  2008, 83(5), 584-594.
[http://dx.doi.org/10.1016/S0025-6196(11)60735-0] [PMID:  18452692] 
[24] 
Liu, S.; Liu, G.; Yi, Y. Novel vanadyl complexes of alginate saccharides: Synthesis, characterization, and biological activities. Carbohydr. Polym.,  2015, 121, 86-91.
[http://dx.doi.org/10.1016/j.carbpol.2014.11.069] [PMID:  25659675] 
[25] 
Zhou, L.; Yi, Y.; Yuan, Q.; Zhang, J.; Li, Y.; Wang, P.; Xu, M.; Xie, S. VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC. Free Radic. Biol. Med.,  2018, 129, 177-185.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.016] [PMID:  30223019] 
[26] 
Han, Q.; Cheng, P.; Yang, H.; Liang, H.; Lin, F. miR-146b reverses epithelial-mesenchymal transition via targeting PTP1B in cisplatin-resistance human lung adenocarcinoma cells. J. Cell. Biochem., 2019. [Online ahead of print
[PMID:  31709623] 
[27] 
Rustgi, A.K.; El-Serag, H.B. Esophageal carcinoma. N. Engl. J. Med.,  2014, 371(26), 2499-2509.
[http://dx.doi.org/10.1056/NEJMra1314530] [PMID:  25539106] 
[28] 
Abnet, C.C.; Arnold, M.; Wei, W.Q. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology,  2018, 154(2), 360-373.
[http://dx.doi.org/10.1053/j.gastro.2017.08.023] [PMID:  28823862] 
[29] 
Warabi, M.; Nemoto, T.; Ohashi, K.; Kitagawa, M.; Hirokawa, K. Expression of protein tyrosine phosphatases and its significance in esophageal cancer. Exp. Mol. Pathol.,  2000, 68(3), 187-195.
[http://dx.doi.org/10.1006/exmp.2000.2303] [PMID:  10816386] 
[30] 
Wang, X.M.; Shang, L.; Zhang, Y.; Hao, J.J.; Shi, F.; Luo, W.; Zhang, T.T.; Wang, B.S.; Yang, Y.; Liu, Z.H.; Zhan, Q.M.; Wang, M.R. PTP1B contributes to calreticulin-induced metastatic phenotypes in esophageal squamous cell carcinoma. Mol. Cancer Res.,  2013, 11(9), 986-994.
[http://dx.doi.org/10.1158/1541-7786.MCR-12-0704] [PMID:  23814025] 
[31] 
Pan, B.Q.; Xie, Z.H.; Hao, J.J.; Zhang, Y.; Xu, X.; Cai, Y.; Wang, M.R. PTP1B up-regulates EGFR expression by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion in esophageal squamous cell carcinoma. Biochem. Biophys. Res. Commun.,  2020, 522(1), 53-60.
[http://dx.doi.org/10.1016/j.bbrc.2019.10.168] [PMID:  31735331] 
[32] 
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID:  30207593] 
[33] 
Wang, J.; Liu, B.; Chen, X.; Su, L.; Wu, P.; Wu, J.; Zhu, Z. PTP1B expression contributes to gastric cancer progression. Med. Oncol.,  2012, 29(2), 948-956.
[http://dx.doi.org/10.1007/s12032-011-9911-2] [PMID:  21442314] 
[34] 
Wang, N.; She, J.; Liu, W.; Shi, J.; Yang, Q.; Shi, B.; Hou, P. Frequent amplification of PTP1B is associated with poor survival of gastric cancer patients. Cell Cycle,  2015, 14(5), 732-743.
[http://dx.doi.org/10.1080/15384101.2014.998047] [PMID:  25590580] 
[35] 
Sun, F.; Yu, M.; Yu, J.; Liu, Z.; Zhou, X.; Liu, Y.; Ge, X.; Gao, H.; Li, M.; Jiang, X.; Liu, S.; Chen, X.; Guan, W. miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis.,  2018, 9(5), 522.
[http://dx.doi.org/10.1038/s41419-018-0611-0] [PMID:  29743567] 
[36] 
Xu, J.; Zhang, Z.; Chen, Q.; Yang, L.; Yin, J. miR-146b regulates cell proliferation and apoptosis in gastric cancer by targeting PTP1B. Dig. Dis. Sci.,  2020, 65(2), 457-463.
[PMID:  31441000] 
[37] 
Yang, S.H.; Seo, M.Y.; Jeong, H.J.; Jeung, H.C.; Shin, J.; Kim, S.C.; Noh, S.H.; Chung, H.C.; Rha, S.Y. Gene copy number change events at chromosome 20 and their association with recurrence in gastric cancer patients. Clin. Cancer Res.,  2005, 11(2 Pt 1), 612-620.
[PMID:  15701848] 
[38] 
Chen, Q.; Li, Y.; Li, Z.; Zhao, Q.; Fan, L. Overexpression of PTP1B in human colorectal cancer and its association with tumor progression and prognosis. J. Mol. Histol.,  2014, 45(2), 153-159.
[http://dx.doi.org/10.1007/s10735-013-9536-1] [PMID:  23990346] 
[39] 
Zhu, S.; Bjorge, J.D.; Fujita, D.J. PTP1B contributes to the oncogenic properties of colon cancer cells through Src activation. Cancer Res.,  2007, 67(21), 10129-10137.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4338] [PMID:  17974954] 
[40] 
Hoekstra, E.; Das, A.M.; Swets, M.; Cao, W.; van der Woude, C.J.; Bruno, M.J.; Peppelenbosch, M.P.; Kuppen, P.J.; Ten Hagen, T.L.; Fuhler, G.M. Increased PTP1B expression and phosphatase activity in colorectal cancer results in a more invasive phenotype and worse patient outcome. Oncotarget,  2016, 7(16), 21922-21938.
[http://dx.doi.org/10.18632/oncotarget.7829] [PMID:  26942883] 
[41] 
Owens, D.K.; Davidson, K.W.; Krist, A.H.; Barry, M.J.; Cabana, M.; Caughey, A.B.; Curry, S.J.; Doubeni, C.A.; Epling, J.W., Jr; Kubik, M.; Landefeld, C.S.; Mangione, C.M.; Pbert, L.; Silverstein, M.; Simon, M.A.; Tseng, C.W.; Wong, J.B.; Wong, J.B. US Preventive Services Task Force. Screening for pancreatic cancer: US preventive services task force reaffirmation recommendation statement. JAMA,  2019, 322(5), 438-444.
[http://dx.doi.org/10.1001/jama.2019.10232] [PMID:  31386141] 
[42] 
Mahlamäki, E.H.; Bärlund, M.; Tanner, M.; Gorunova, L.; Höglund, M.; Karhu, R.; Kallioniemi, A. Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chromosomes Cancer,  2002, 35(4), 353-358.
[http://dx.doi.org/10.1002/gcc.10122] [PMID:  12378529] 
[43] 
Rawla, P.; Sunkara, T.; Gaduputi, V. Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J. Oncol.,  2019, 10(1), 10-27.
[http://dx.doi.org/10.14740/wjon1166] [PMID:  30834048] 
[44] 
Xu, Q.; Wu, N.; Li, X.; Guo, C.; Li, C.; Jiang, B.; Wang, H.; Shi, D. Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway. Cell Death Dis.,  2019, 10(12), 874.
[http://dx.doi.org/10.1038/s41419-019-2073-4] [PMID:  31745071] 
[45] 
Carmona, S.; Brunel, J.M.; Bonier, R.; Sbarra, V.; Robert, S.; Borentain, P.; Lombardo, D.; Mas, E.; Gerolami, R. A squalamine derivative, NV669, as a novel PTP1B inhibitor: in vitro and in vivo effects on pancreatic and hepatic tumor growth. Oncotarget,  2019, 10(62), 6651-6667.
[http://dx.doi.org/10.18632/oncotarget.27286] [PMID:  31803360] 
[46] 
Singal, A.G.; Lampertico, P.; Nahon, P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J. Hepatol.,  2020, 72(2), 250-261.
[http://dx.doi.org/10.1016/j.jhep.2019.08.025] [PMID:  31954490] 
[47] 
Villanueva, A. Hepatocellular carcinoma. N. Engl. J. Med.,  2019, 380(15), 1450-1462.
[http://dx.doi.org/10.1056/NEJMra1713263] [PMID:  30970190] 
[48] 
Zheng, L.Y.; Zhou, D.X.; Lu, J.; Zhang, W.J.; Zou, D.J. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma. Biochem. Biophys. Res. Commun.,  2012, 420(3), 680-684.
[http://dx.doi.org/10.1016/j.bbrc.2012.03.066] [PMID:  22450318] 
[49] 
Tai, W.T.; Chen, Y.L.; Chu, P.Y.; Chen, L.J.; Hung, M.H.; Shiau, C.W.; Huang, J.W.; Tsai, M.H.; Chen, K.F. Protein tyrosine phosphatase 1B dephosphorylates PITX1 and regulates p120RasGAP in hepatocellular carcinoma. Hepatology,  2016, 63(5), 1528-1543.
[http://dx.doi.org/10.1002/hep.28478] [PMID:  26840794] 
[50] 
Yang, Q.; Zhang, L.; Zhong, Y.; Lai, L.; Li, X. miR-206 inhibits cell proliferation, invasion, and migration by down-regulating PTP1B in hepatocellular carcinoma. Biosci. Rep.,  2019, 39(5), BSR20181823.
[http://dx.doi.org/10.1042/BSR20181823] [PMID:  31048362] 
[51] 
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin.,  2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID:  30620402] 
[52] 
Dalgliesh, G.L.; Furge, K.; Greenman, C.; Chen, L.; Bignell, G.; Butler, A.; Davies, H.; Edkins, S.; Hardy, C.; Latimer, C.; Teague, J.; Andrews, J.; Barthorpe, S.; Beare, D.; Buck, G.; Campbell, P.J.; Forbes, S.; Jia, M.; Jones, D.; Knott, H.; Kok, C.Y.; Lau, K.W.; Leroy, C.; Lin, M.L.; McBride, D.J.; Maddison, M.; Maguire, S.; McLay, K.; Menzies, A.; Mironenko, T.; Mulderrig, L.; Mudie, L.; O’Meara, S.; Pleasance, E.; Rajasingham, A.; Shepherd, R.; Smith, R.; Stebbings, L.; Stephens, P.; Tang, G.; Tarpey, P.S.; Turrell, K.; Dykema, K.J.; Khoo, S.K.; Petillo, D.; Wondergem, B.; Anema, J.; Kahnoski, R.J.; Teh, B.T.; Stratton, M.R.; Futreal, P.A. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature,  2010, 463(7279), 360-363.
[http://dx.doi.org/10.1038/nature08672] [PMID:  20054297] 
[53] 
Liu, X.; Chen, Q.; Hu, X.G.; Zhang, X.C.; Fu, T.W.; Liu, Q.; Liang, Y.; Zhao, X.L.; Zhang, X.; Ping, Y.F.; Bian, X.W. PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT. Tumour Biol.,  2016, 37(10), 13479-13487.
[http://dx.doi.org/10.1007/s13277-016-5245-1] [PMID:  27465552] 
[54] 
Liao, S.C.; Li, J.X.; Yu, L.; Sun, S.R. Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer. J. Zhejiang Univ. Sci. B,  2017, 18(4), 334-342.
[http://dx.doi.org/10.1631/jzus.B1600184] [PMID:  28378571] 
[55] 
Wiener, J.R.; Kerns, B.J.; Harvey, E.L.; Conaway, M.R.; Iglehart, J.D.; Berchuck, A.; Bast, R.C., Jr Overexpression of the protein tyrosine phosphatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression. J. Natl. Cancer Inst.,  1994, 86(5), 372-378.
[http://dx.doi.org/10.1093/jnci/86.5.372] [PMID:  7905928] 
[56] 
Yu, M.; Liu, Z.; Liu, Y.; Zhou, X.; Sun, F.; Liu, Y.; Li, L.; Hua, S.; Zhao, Y.; Gao, H.; Zhu, Z.; Na, M.; Zhang, Q.; Yang, R.; Zhang, J.; Yao, Y.; Chen, X. PTP1B markedly promotes breast cancer progression and is regulated by miR-193a-3p. FEBS J.,  2019, 286(6), 1136-1153.
[http://dx.doi.org/10.1111/febs.14724] [PMID:  30548198] 
[57] 
Li, Y.; Zeng, Q.; Qiu, J.; Pang, T.; Xian, J.; Zhang, X. Long non-coding RNA UCA1 promotes breast cancer by upregulating PTP1B expression via inhibiting miR-206. Cancer Cell Int.,  2019, 19, 275.
[http://dx.doi.org/10.1186/s12935-019-0958-z] [PMID:  31695578] 
[58] 
Julien, S.G.; Dubé, N.; Read, M.; Penney, J.; Paquet, M.; Han, Y.; Kennedy, B.P.; Muller, W.J.; Tremblay, M.L. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat. Genet.,  2007, 39(3), 338-346.
[http://dx.doi.org/10.1038/ng1963] [PMID:  17259984] 
[59] 
Balavenkatraman, K.K.; Aceto, N.; Britschgi, A.; Mueller, U.; Bence, K.K.; Neel, B.G.; Bentires-Alj, M. Epithelial protein-tyrosine phosphatase 1B contributes to the induction of mammary tumors by HER2/Neu but is not essential for tumor maintenance. Mol. Cancer Res.,  2011, 9(10), 1377-1384.
[http://dx.doi.org/10.1158/1541-7786.MCR-11-0198] [PMID:  21849469] 
[60] 
Bentires-Alj, M.; Neel, B.G. Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res.,  2007, 67(6), 2420-2424.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4610] [PMID:  17347513] 
[61] 
Banh, R.S.; Iorio, C.; Marcotte, R.; Xu, Y.; Cojocari, D.; Rahman, A.A.; Pawling, J.; Zhang, W.; Sinha, A.; Rose, C.M.; Isasa, M.; Zhang, S.; Wu, R.; Virtanen, C.; Hitomi, T.; Habu, T.; Sidhu, S.S.; Koizumi, A.; Wilkins, S.E.; Kislinger, T.; Gygi, S.P.; Schofield, C.J.; Dennis, J.W.; Wouters, B.G.; Neel, B.G. PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia. Nat. Cell Biol.,  2016, 18(7), 803-813.
[http://dx.doi.org/10.1038/ncb3376] [PMID:  27323329] 
[62] 
Blanquart, C.; Karouri, S.E.; Issad, T. Protein tyrosine phosphatase-1B and T-cell protein tyrosine phosphatase regulate IGF-2-induced MCF-7 cell migration. Biochem. Biophys. Res. Commun.,  2010, 392(1), 83-88.
[http://dx.doi.org/10.1016/j.bbrc.2009.12.176] [PMID:  20059965] 
[63] 
Blanquart, C.; Karouri, S.E.; Issad, T. Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen. Biochem. Biophys. Res. Commun.,  2009, 387(4), 748-753.
[http://dx.doi.org/10.1016/j.bbrc.2009.07.105] [PMID:  19635455] 
[64] 
Arias-Romero, L.E.; Saha, S.; Villamar-Cruz, O.; Yip, S.C.; Ethier, S.P.; Zhang, Z.Y.; Chernoff, J. Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells. Cancer Res.,  2009, 69(11), 4582-4588.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4001] [PMID:  19435911] 
[65] 
Bjorge, J.D.; Pang, A.; Fujita, D.J. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J. Biol. Chem.,  2000, 275(52), 41439-41446.
[http://dx.doi.org/10.1074/jbc.M004852200] [PMID:  11007774] 
[66] 
Cortesio, C.L.; Chan, K.T.; Perrin, B.J.; Burton, N.O.; Zhang, S.; Zhang, Z-Y.; Huttenlocher, A. Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion. J. Cell Biol.,  2008, 180(5), 957-971.
[http://dx.doi.org/10.1083/jcb.200708048] [PMID:  18332219] 
[67] 
Johnson, K.J.; Peck, A.R.; Liu, C.; Tran, T.H.; Utama, F.E.; Sjolund, A.B.; Schaber, J.D.; Witkiewicz, A.K.; Rui, H. PTP1B suppresses prolactin activation of Stat5 in breast cancer cells. Am. J. Pathol.,  2010, 177(6), 2971-2983.
[http://dx.doi.org/10.2353/ajpath.2010.090399] [PMID:  20952588] 
[68] 
Yuan, C.; Wang, W.; Wang, J.; Li, X.; Wu, Y.B.; Li, S.; Lu, L.; Zhu, M.; Xing, S.; Fu, X. Potent and selective PTP1B inhibition by a platinum(ii) complex: Possible implications for a new antitumor strategy. Chem. Commun. (Camb.),  2019, 56(1), 102-105.
[http://dx.doi.org/10.1039/C9CC06972K] [PMID:  31793564] 
[69] 
Kuban-Jankowska, A.; Gorska-Ponikowska, M.; Sahu, K.K.; Kostrzewa, T.; Wozniak, M.; Tuszynski, J. Docosahexaenoic acid inhibits PTP1B phosphatase and the viability of MCF-7 breast cancer cells. Nutrients,  2019, 11(11), E2554.
[http://dx.doi.org/10.3390/nu11112554] [PMID:  31652764] 
[70] 
Soysal, S.; Obermann, E.C.; Gao, F.; Oertli, D.; Gillanders, W.E.; Viehl, C.T.; Muenst, S. PTP1B expression is an independent positive prognostic factor in human breast cancer. Breast Cancer Res. Treat.,  2013, 137(2), 637-644.
[http://dx.doi.org/10.1007/s10549-012-2373-1] [PMID:  23242616] 
[71] 
Hughes, S.K.; Oudin, M.J.; Tadros, J.; Neil, J.; Del Rosario, A.; Joughin, B.A.; Ritsma, L.; Wyckoff, J.; Vasile, E.; Eddy, R.; Philippar, U.; Lussiez, A.; Condeelis, J.S.; van Rheenen, J.; White, F.; Lauffenburger, D.A.; Gertler, F.B. PTP1B-dependent regulation of receptor tyrosine kinase signaling by the actin-binding protein Mena. Mol. Biol. Cell,  2015, 26(21), 3867-3878.
[http://dx.doi.org/10.1091/mbc.E15-06-0442] [PMID:  26337385] 
[72] 
Taliaferro-Smith, L.; Nagalingam, A.; Knight, B.B.; Oberlick, E.; Saxena, N.K.; Sharma, D. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis. Neoplasia,  2013, 15(1), 23-38.
[http://dx.doi.org/10.1593/neo.121502] [PMID:  23358729] 
[73] 
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer,  2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID:  25220842] 
[74] 
Reid, B.M.; Permuth, J.B.; Sellers, T.A. Epidemiology of ovarian cancer: A review. Cancer Biol. Med.,  2017, 14(1), 9-32.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0084] [PMID:  28443200] 
[75] 
Carlson, K.J.; Skates, S.J.; Singer, D.E. Screening for ovarian cancer. Ann. Intern. Med.,  1994, 121(2), 124-132.
[http://dx.doi.org/10.7326/0003-4819-121-2-199407150-00009] [PMID:  8017726] 
[76] 
Fan, G.; Lin, G.; Lucito, R.; Tonks, N.K. Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells. J. Biol. Chem.,  2013, 288(34), 24923-24934.
[http://dx.doi.org/10.1074/jbc.M113.482737] [PMID:  23814047] 
[77] 
Fang, X.; Schummer, M.; Mao, M.; Yu, S.; Tabassam, F.H.; Swaby, R.; Hasegawa, Y.; Tanyi, J.L.; LaPushin, R.; Eder, A.; Jaffe, R.; Erickson, J.; Mills, G.B. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim. Biophys. Acta,  2002, 1582(1-3), 257-264.
[http://dx.doi.org/10.1016/S1388-1981(02)00179-8] [PMID:  12069836] 
[78] 
Huang, R.Y.; Wen, C.C.; Liao, C.K.; Wang, S.H.; Chou, L.Y.; Wu, J.C. Lysophosphatidic acid modulates the association of PTP1B with N-cadherin/catenin complex in SKOV3 ovarian cancer cells. Cell Biol. Int.,  2012, 36(9), 833-841.
[http://dx.doi.org/10.1042/CBI20110687] [PMID:  22582758] 
[79] 
Wang, W.; Cao, Y.; Zhou, X.; Wei, B.; Zhang, Y.; Liu, X. PTP1B promotes the malignancy of ovarian cancer cells in a JNK-dependent mechanism. Biochem. Biophys. Res. Commun.,  2018, 503(2), 903-909.
[http://dx.doi.org/10.1016/j.bbrc.2018.06.094] [PMID:  29928877] 
[80] 
Wiener, J.R.; Hurteau, J.A.; Kerns, B.J.; Whitaker, R.S.; Conaway, M.R.; Berchuck, A.; Bast, R.C., Jr Overexpression of the tyrosine phosphatase PTP1B is associated with human ovarian carcinomas. Am. J. Obstet. Gynecol.,  1994, 170(4), 1177-1183.
[http://dx.doi.org/10.1016/S0002-9378(94)70118-0] [PMID:  8166206] 
[81] 
Pariza, M.W.; Ha, Y.L. Conjugated dienoic derivatives of linoleic acid: A new class of anticarcinogens. Med. Oncol. Tumor Pharmacother.,  1990, 7(2-3), 169-171.
[http://dx.doi.org/10.1007/BF02988544] [PMID:  2232933] 
[82] 
Shahzad, M.M.K.; Felder, M.; Ludwig, K.; Van Galder, H.R.; Anderson, M.L.; Kim, J.; Cook, M.E.; Kapur, A.K.; Patankar, M.S. Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src. PLoS One,  2018, 13(1), e0189524.
[http://dx.doi.org/10.1371/journal.pone.0189524] [PMID:  29324748] 
[83] 
Lessard, L.; Labbé, D.P.; Deblois, G.; Bégin, L.R.; Hardy, S.; Mes-Masson, A.M.; Saad, F.; Trotman, L.C.; Giguère, V.; Tremblay, M.L. PTP1B is an androgen receptor-regulated phosphatase that promotes the progression of prostate cancer. Cancer Res.,  2012, 72(6), 1529-1537.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-2602] [PMID:  22282656] 
[84] 
Bar-Shira, A.; Pinthus, J.H.; Rozovsky, U.; Goldstein, M.; Sellers, W.R.; Yaron, Y.; Eshhar, Z.; Orr-Urtreger, A. Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft. Cancer Res.,  2002, 62(23), 6803-6807.
[PMID:  12460888] 
[85] 
Wu, C.; Zhang, L.; Bourne, P.A.; Reeder, J.E.; di Sant’Agnese, P.A.; Yao, J.L.; Na, Y.; Huang, J. Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation of prostate cancer. Prostate,  2006, 66(11), 1125-1135.
[http://dx.doi.org/10.1002/pros.20412] [PMID:  16652382] 
[86] 
Labbé, D.P.; Uetani, N.; Vinette, V.; Lessard, L.; Aubry, I.; Migon, E.; Sirois, J.; Haigh, J.J.; Bégin, L.R.; Trotman, L.C.; Paquet, M.; Tremblay, M.L. PTP1B deficiency enables the ability of a high-fat diet to drive the invasive character of PTEN-deficient prostate cancers. Cancer Res.,  2016, 76(11), 3130-3135.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1501] [PMID:  27020859] 
[87] 
Lee, Y-J.; Song, H.; Yoon, Y.J.; Park, S-J.; Kim, S-Y.; Cho Han, D.; Kwon, B-M. Ethacrynic acid inhibits STAT3 activity through the modulation of SHP2 and PTP1B tyrosine phosphatases in DU145 prostate carcinoma cells. Biochem. Pharmacol.,  2020, 175, 113920.
[http://dx.doi.org/10.1016/j.bcp.2020.113920] [PMID:  32201212] 
[88] 
Mugnaini, E.N.; Ghosh, N. Lymphoma. Prim. Care,  2016, 43(4), 661-675.
[http://dx.doi.org/10.1016/j.pop.2016.07.012] [PMID:  27866584] 
[89] 
Chung, C. Current targeted therapies in lymphomas. American journal of health-system pharmacy: AJHP,  2019, 76(22), 1825-1834.
[90] 
Lu, X.; Malumbres, R.; Shields, B.; Jiang, X.; Sarosiek, K.A.; Natkunam, Y.; Tiganis, T.; Lossos, I.S. PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling. Blood,  2008, 112(10), 4098-4108.
[http://dx.doi.org/10.1182/blood-2008-03-148726] [PMID:  18716132] 
[91] 
Zahn, M.; Marienfeld, R.; Melzner, I.; Heinrich, J.; Renner, B.; Wegener, S.; Mießner, A.; Barth, T.F.; Dorsch, K.; Brüderlein, S.; Möller, P. A novel PTPN1 splice variant upregulates JAK/STAT activity in classical Hodgkin lymphoma cells. Blood,  2017, 129(11), 1480-1490.
[http://dx.doi.org/10.1182/blood-2016-06-720516] [PMID:  28082443] 
[92] 
Gunawardana, J.; Chan, F.C.; Telenius, A.; Woolcock, B.; Kridel, R.; Tan, K.L.; Ben-Neriah, S.; Mottok, A.; Lim, R.S.; Boyle, M.; Rogic, S.; Rimsza, L.M.; Guiter, C.; Leroy, K.; Gaulard, P.; Haioun, C.; Marra, M.A.; Savage, K.J.; Connors, J.M.; Shah, S.P.; Gascoyne, R.D.; Steidl, C. Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nat. Genet.,  2014, 46(4), 329-335.
[http://dx.doi.org/10.1038/ng.2900] [PMID:  24531327] 
[93] 
Dubé, N.; Bourdeau, A.; Heinonen, K.M.; Cheng, A.; Loy, A.L.; Tremblay, M.L. Genetic ablation of protein tyrosine phosphatase 1B accelerates lymphomagenesis of p53-null mice through the regulation of B-cell development. Cancer Res.,  2005, 65(21), 10088-10095.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1353] [PMID:  16267035] 
[94] 
Jacks, T.; Remington, L.; Williams, B.O.; Schmitt, E.M.; Halachmi, S.; Bronson, R.T.; Weinberg, R.A. Tumor spectrum analysis in p53-mutant mice. Curr. Biol.,  1994, 4(1), 1-7.
[http://dx.doi.org/10.1016/S0960-9822(00)00002-6] [PMID:  7922305] 
[95] 
Zhu, F.; Wang, K.B.; Rui, L. STAT3 activation and oncogenesis in lymphoma. Cancers (Basel),  2019, 12(1), E19.
[http://dx.doi.org/10.3390/cancers12010019] [PMID:  31861597] 
[96] 
Vainchenker, W.; Constantinescu, S.N. JAK/STAT signaling in hematological malignancies. Oncogene,  2013, 32(21), 2601-2613.
[http://dx.doi.org/10.1038/onc.2012.347] [PMID:  22869151] 
[97] 
Waldmann, T.A.; Chen, J. Disorders of the JAK/STAT pathway in T cell lymphoma pathogenesis: implications for immunotherapy. Annu. Rev. Immunol.,  2017, 35, 533-550.
[http://dx.doi.org/10.1146/annurev-immunol-110416-120628] [PMID:  28182501] 
[98] 
Zhao, B.; Zhang, Z.; Chen, X.; Shen, Y.; Qin, Y.; Yang, X.; Xing, Z.; Zhang, S.; Long, X.; Zhang, Y.; An, S.; Wu, H.; Qi, Y. The important roles of protein SUMOylation in the occurrence and development of leukemia and clinical implications. J. Cell. Physiol.,  2020, 236(5), 3466-3480.
[PMID:  33151565] 
[99] 
Blackburn, L.M.; Bender, S.; Brown, S. Acute leukemia: Diagnosis and treatment. Semin. Oncol. Nurs.,  2019, 35(6), 150950.
[http://dx.doi.org/10.1016/j.soncn.2019.150950] [PMID:  31757585] 
[100] 
Le Sommer, S.; Morrice, N.; Pesaresi, M.; Thompson, D.; Vickers, M.A.; Murray, G.I.; Mody, N.; Neel, B.G.; Bence, K.K.; Wilson, H.M.; Delibegović, M. Deficiency in protein tyrosine phosphatase PTP1B shortens lifespan and leads to development of acute leukemia. Cancer Res.,  2018, 78(1), 75-87.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0946] [PMID:  29122767] 
[101] 
LaMontagne, K.R., Jr; Flint, A.J.; Franza, B.R., Jr; Pandergast, A.M.; Tonks, N.K. Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine kinase p210 BCR-ABL in vivo. Mol. Cell. Biol.,  1998, 18(5), 2965-2975.
[http://dx.doi.org/10.1128/MCB.18.5.2965] [PMID:  9566916] 
[102] 
LaMontagne, K.R., Jr; Hannon, G.; Tonks, N.K. Protein tyrosine phosphatase PTP1B suppresses p210 BCR-ABL-induced transformation of rat-1 fibroblasts and promotes differentiation of K562 cells. Proc. Natl. Acad. Sci. USA,  1998, 95(24), 14094-14099.
[http://dx.doi.org/10.1073/pnas.95.24.14094] [PMID:  9826659] 
[103] 
Goldman, J.M.; Melo, J.V. BCR-ABL in chronic myelogenous leukemia-how does it work? Acta Haematol.,  2008, 119(4), 212-217.
[http://dx.doi.org/10.1159/000140633] [PMID:  18566539] 
[104] 
Koyama, N.; Koschmieder, S.; Tyagi, S.; Portero-Robles, I.; Chromic, J.; Myloch, S.; Nürnberger, H.; Rossmanith, T.; Hofmann, W.K.; Hoelzer, D.; Ottmann, O.G. Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL-positive leukemia cells to the ABL kinase inhibitor STI571. Clin. Cancer Res.,  2006, 12(7 Pt 1), 2025-2031.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2392] [PMID:  16609011] 
[105] 
Alvira, D.; Naughton, R.; Bhatt, L.; Tedesco, S.; Landry, W.D.; Cotter, T.G. Inhibition of protein-tyrosine phosphatase 1B (PTP1B) mediates ubiquitination and degradation of BCR-ABL protein. J. Biol. Chem.,  2011, 286(37), 32313-32323.
[http://dx.doi.org/10.1074/jbc.M111.249060] [PMID:  21795709] 
[106] 
Elgehama, A.; Chen, W.; Pang, J.; Mi, S.; Li, J.; Guo, W.; Wang, X.; Gao, J.; Yu, B.; Shen, Y.; Xu, Q. Blockade of the interaction between BCR-ABL and PTB1B by small molecule SBF-1 to overcome imatinib-resistance of chronic myeloid leukemia cells. Cancer Lett.,  2016, 372(1), 82-88.
[http://dx.doi.org/10.1016/j.canlet.2015.12.014] [PMID:  26721204] 
Cite As
Current Cancer Drug Targets

Protein Tyrosine Phosphatase 1B (PTP1B): Insights into its New Implications in Tumorigenesis

Abstract

Graphical Abstract
