PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival

Jin,Tao; Li,Dongbo; Yang,Tao; Liu,Feng; Kong,Juan; Zhou,Yuefei

doi:10.3892/or.2019.7180

PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival

Authors:
- Tao Jin
- Dongbo Li
- Tao Yang
- Feng Liu
- Juan Kong
- Yuefei Zhou
View Affiliations

Affiliations: Department of Neurosurgery, Ankang Central Hospital, Ankang, Shaanxi 725000, P.R. China, Department of General Practice, Zhoukou Central Hospital, Zhoukou, Henan 466000, P.R. China, Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: May 31, 2019 https://doi.org/10.3892/or.2019.7180
Pages: 717-725

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glioma is the most common primary brain tumor and is characterized by a poor prognosis. Protein tyrosine phosphatase 1B (PTPN1), as a non‑transmembrane protein tyrosine phosphatase, has been reported to serve a critical role in different diseases, including cancer. However, the role of PTPN1 in the progression of glioma remains unclear. The present study investigated the expression and clinicopathological characteristics of PTPN1 by analyzing the data from The Cancer Genome Atlas and 136 patients with glioma. It was indicated that PTPN1 was overexpressed in glioma tissues and served as a predictor for poor prognosis in patients with glioma. In addition, a series of in vitro experiments were performed to examine the underlying mechanism of PTPN1 overexpression and the clinical prognosis in patients with glioma. Knockdown of PTPN1 by small interfering RNA suppressed proliferation of glioma cells, including SF295 and A172. In addition, cell mobility was also inhibited by PTPN1 knockdown, downregulating the expression of matrix metallopeptidase 2 (MMP‑2) and MMP‑9. As indicated by western blot analysis, the mitogen‑activated protein kinase (MAPK)/extracellular‑signal‑regulated kinase (ERK) signaling pathway and the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was regulated by PTPN1, while knockdown of PTPN1 significantly suppressed the MAPK/ERK and PI3K/AKT pathways, in addition to the downstream oncogenic transcription factor MYC Proto‑Oncogene. In conclusion, it was demonstrated that PTPN1 is upregulated in glioma tissue and the overexpression of PTPN1 predicted the poor prognosis of patients with glioma. PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways.

View Figures

View References

1	Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, et al: Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. J Clin Oncol. 28:1963–1972. 2010. View Article : Google Scholar : PubMed/NCBI
2	Mittal S, Pradhan S and Srivastava T: Recent advances in targeted therapy for glioblastoma. Expert Rev Neurother. 15:935–946. 2015. View Article : Google Scholar : PubMed/NCBI
3	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
4	Huse JT and Holland EC: Targeting brain cancer: Advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 10:319–331. 2010. View Article : Google Scholar : PubMed/NCBI
5	Seely BL, Staubs PA, Reichart DR, Berhanu P, Milarski KL, Saltiel AR, Kusari J and Olefsky JM: Protein tyrosine phosphatase 1B interacts with the activated insulin receptor. Diabetes. 45:1379–1385. 1996. View Article : Google Scholar : PubMed/NCBI
6	Lessard L, Stuible M and Tremblay ML: The two faces of PTP1B in cancer. Biochim Biophys Acta. 1804:613–619. 2010. View Article : Google Scholar : PubMed/NCBI
7	Cortesio CL, Chan KT, Perrin BJ, Burton NO, Zhang S, Zhang ZY and 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. 180:957–971. 2008. View Article : Google Scholar : PubMed/NCBI
8	Liu H, Wu Y, Zhu S, Liang W, Wang Z, Wang Y, Lv T, Yao Y, Yuan D and Song Y: PTP1B promotes cell proliferation and metastasis through activating src and ERK1/2 in non-small cell lung cancer. Cancer Lett. 359:218–225. 2015. View Article : Google Scholar : PubMed/NCBI
9	LaMontagne KR Jr, Hannon G and Tonks NK: Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of rat-1 fibroblasts and promotes differentiation of K562 cells. Proc NatI Acad Sci USA. 95:14094–14099. 1998. View Article : Google Scholar
10	Balsamo J, Leung T, Ernst H, Zanin MK, Hoffman S and Lilien J: Regulated binding of PTP1B-like phosphatase to N-cadherin: Control of cadherin-mediated adhesion by dephosphorylation of beta-catenin. J Cell Biol. 134:801–813. 1996. View Article : Google Scholar : PubMed/NCBI
11	Chen H, Chen W, Zhang X, Hu L, Tang G, Kong J and Wang Z: E26 transformation (ETS)-specific related transcription factor-3 (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer. Oncol Rep. 41:570–578. 2019.PubMed/NCBI
12	Wu G, Mambo E, Guo Z, Hu S, Huang X, Gollin SM, Trink B, Ladenson PW, Sidransky D and Xing M: Uncommon mutation, but common amplifications of the PIK3CA gene in thyroid tumors. J Clin Endocrinol Metab. 90:4688–4693. 2005. View Article : Google Scholar : PubMed/NCBI
13	Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 316:1039–1043. 2007. View Article : Google Scholar : PubMed/NCBI
14	Kawano O, Sasaki H, Okuda K, Yukiue H, Yokoyama T, Yano M and Fujii Y: PIK3CA gene amplification in Japanese non-small cell lung cancer. Lung Cancer. 58:159–160. 2007. View Article : Google Scholar : PubMed/NCBI
15	Mambo E, Gao X, Cohen Y, Guo Z, Talalay P and Sidransky D: Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations. Proce Natl Acad Sci USA. 100:1838–1843. 2003. View Article : Google Scholar
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
18	Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI
19	Guha A, Feldkamp MM, Lau N, Boss G and Pawson A: Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene. 15:2755–2765. 1997. View Article : Google Scholar : PubMed/NCBI
20	Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzàlez-Juncà A, Sodir NM, et al: Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat Commun. 5:46322014. View Article : Google Scholar : PubMed/NCBI
21	Tu M, Wange W, Cai L, Zhu P, Gao Z and Zheng W: IL-13 receptor alpha2 stimulates human glioma cell growth and metastasis through the Src/PI3K/Akt/mTOR signaling pathway. Tumour Biol. 37:14701–14709. 2016. View Article : Google Scholar : PubMed/NCBI
22	Zhang X, Chen T, Zhang J, Mao Q, Li S, Xiong W, Qiu Y, Xie Q and Ge J: Notch1 promotes glioma cell migration and invasion by stimulating beta-catenin and NF-kappaB signaling via AKT activation. Cancer Sci. 103:181–190. 2012. View Article : Google Scholar : PubMed/NCBI
23	Taliaferro-Smith L, Nagalingam A, Knight BB, Oberlick E, Saxena NK and Sharma D: Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis. Neoplasia. 15:23–38. 2013. View Article : Google Scholar : PubMed/NCBI
24	Wang J, Liu B, Chen X, Su L, Wu P, Wu J and Zhu Z: PTP1B expression contributes to gastric cancer progression. Med Oncol. 29:948–956. 2012. View Article : Google Scholar : PubMed/NCBI
25	Reichardt W, Jung V, Brunner C, Klein A, Wemmert S, Romeike BF, Zang KD and Urbschat S: The putative serine/threonine kinase gene STK15 on chromosome 20q13.2 is amplified in human gliomas. Oncol Rep. 10:1275–1279. 2003.PubMed/NCBI
26	Mondol AS, Tonks NK and Kamata T: Nox4 redox regulation of PTP1B contributes to the proliferation and migration of glioblastoma cells by modulating tyrosine phosphorylation of coronin-1C. Free Radic Biol Med. 67:285–291. 2014. View Article : Google Scholar : PubMed/NCBI
27	Akasaki Y, Liu G, Matundan HH, Ng H, Yuan X, Zeng Z, Black KL and Yu JS: A peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and −9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells. J Biol Chem. 281:6165–6174. 2006. View Article : Google Scholar : PubMed/NCBI
28	Petri MK, Koch P, Stenzinger A, Kuchelmeister K, Nestler U, Paradowska A, Steger K, Brobeil A, Viard M and Wimmer M: PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14–3-3β and PTP1B in situ. Histol Histopathol. 26:1531–1543. 2011.PubMed/NCBI
29	Zhu S, Bjorge JD and Fujita DJ: PTP1B contributes to the oncogenic properties of colon cancer cells through Src activation. Cancer Res. 67:10129–10137. 2007. View Article : Google Scholar : PubMed/NCBI
30	Chen T, George JA and Taylor CC: Src tyrosine kinase as a chemotherapeutic target: Is there a clinical case? Anticancer Drugs. 17:123–131. 2006. View Article : Google Scholar : PubMed/NCBI
31	Wang J, Zhang Z, Li R, Mao F, Sun W, Chen J, Zhang H, Bartsch JW, Shu K and Lei T: ADAM12 induces EMT and promotes cell migration, invasion and proliferation in pituitary adenomas via EGFR/ERK signaling pathway. Biomed Pharmacother. 97:1066–1077. 2018. View Article : Google Scholar : PubMed/NCBI
32	Du MR, Zhou WH, Yan FT, Zhu XY, He YY, Yang JY and Li DJ: Cyclosporine A induces titin expression via MAPK/ERK signalling and improves proliferative and invasive potential of human trophoblast cells. Hum Reprod. 22:2528–2537. 2007. View Article : Google Scholar : PubMed/NCBI
33	Huang HY, Chang HF, Tsai MJ, Chen JS and Wang MJ: 6-Mercaptopurine attenuates tumor necrosis factor-alpha production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation. J Neuroinflammation. 13:782016. View Article : Google Scholar : PubMed/NCBI
34	Butowski NA and Chang SM: Glial tumors: The current state of scientific knowledge. Clin Neurosurg. 53:106–113. 2006.PubMed/NCBI
35	Purow BW, Sundaresan TK, Burdick MJ, Kefas BA, Comeau LD, Hawkinson MP, Su Q, Kotliarov Y, Lee J, Zhang W and Fine HA: Notch-1 regulates transcription of the epidermal growth factor receptor through p53. Carcinogenesis. 29:918–925. 2008. View Article : Google Scholar : PubMed/NCBI
36	Guo G, Yao W, Zhang Q and Bo Y: Oleanolic acid suppresses migration and invasion of malignant glioma cells by inactivating MAPK/ERK signaling pathway. PLoS One. 8:e720792013. View Article : Google Scholar : PubMed/NCBI
37	Hollander MC, Blumenthal GM and Dennis PA: PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer. 11:289–301. 2011. View Article : Google Scholar : PubMed/NCBI
38	Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI
39	Chai C, Song LJ, Han SY, Li XQ and Li M: MicroRNA-21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway. CNS Neurosci Ther. 24:369–380. 2018. View Article : Google Scholar : PubMed/NCBI
40	Jiang L, Wang Z, Liu C, Gong Z, Yang Y, Kang H, Li Y and Hu G: TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway. Oncotarget. 8:108726–108737. 2017. View Article : Google Scholar : PubMed/NCBI
41	Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM, et al: Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 164:550–563. 2016. View Article : Google Scholar : PubMed/NCBI