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

  • Published online on: May 31, 2019     https://doi.org/10.3892/or.2019.7180
  • Pages: 717-725
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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.

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

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August 2019
Volume 42 Issue 2

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Copy and paste a formatted citation
APA
Jin, T., Li, D., Yang, T., Liu, F., Kong, J., & Zhou, Y. (2019). PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival. Oncology Reports, 42, 717-725. https://doi.org/10.3892/or.2019.7180
MLA
Jin, T., Li, D., Yang, T., Liu, F., Kong, J., Zhou, Y."PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival". Oncology Reports 42.2 (2019): 717-725.
Chicago
Jin, T., Li, D., Yang, T., Liu, F., Kong, J., Zhou, Y."PTPN1 promotes the progression of glioma by activating the MAPK/ERK and PI3K/AKT pathways and is associated with poor patient survival". Oncology Reports 42, no. 2 (2019): 717-725. https://doi.org/10.3892/or.2019.7180