CIP2A regulates cell proliferation via the AKT signaling pathway in human lung cancer

Lei,Ningjing; Peng,Bo; Zhang,Jian-Ying

doi:10.3892/or.2014.3375

CIP2A regulates cell proliferation via the AKT signaling pathway in human lung cancer

Authors:
- Ningjing Lei
- Bo Peng
- Jian-Ying Zhang
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Affiliations: Border Biomedical Research Center and Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA
Published online on: August 1, 2014 https://doi.org/10.3892/or.2014.3375
Pages: 1689-1694

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Abstract

Cancerous inhibitor of PP2A (CIP2A) is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. Initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, CIP2A was overexpressed in a variety of cancer types. The overexpression of CIP2A in cancer cells is associated with increased cell proliferation. However, the mechanism of CIP2A in cancer cell proliferation remains poorly understood. In the present study, we reported that CIP2A can regulate AKT phosphorylation at S473 under growth factor stimulation and our results also showed that CIP2A may promote cell proliferation through the AKT signaling pathway. Notably, depletion of CIP2A did not induce a global change of AKT phosphatase activity, which indicated that CIP2A may recognize specific AKT targets and play certain roles in the signaling pathway. In addition, we detected that CIP2A expression was associated with mTOR phosphorylation. Our further analysis corroborated the relationship between CIP2A and AKT-mTOR signaling pathway. Therefore, our study addressed a novel role of CIP2A in mediating cancer progression through interacting with the AKT-mTOR signaling pathway.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar
2	Travis WD, Travis LB and Devesa SS: Lung cancer. Cancer. 75(Suppl 1): 191–202. 1995. View Article : Google Scholar : PubMed/NCBI
3	Fong KM, Sekido Y, Gazdar AF and Minna JD: Lung cancer. 9: Molecular biology of lung cancer: clinical implications. Thorax. 58:892–900. 2003. View Article : Google Scholar : PubMed/NCBI
4	Aviel-Ronen S, Blackhall FH, Shepherd FA and Tsao MS: K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer. 8:30–38. 2006.
5	Haura EB, Camidge DR, Reckamp K, et al: Molecular origins of lung cancer: prospects for personalized prevention and therapy. J Thorac Oncol. 5(Suppl 3): S207–S213. 2010. View Article : Google Scholar
6	Huff V: Wilms’ tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer. 11:111–121. 2011.
7	Shackelford DB and Shaw RJ: The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 9:563–575. 2009. View Article : Google Scholar : PubMed/NCBI
8	Soo Hoo L, Zhang JY and Chan EK: Cloning and characterization of a novel 90 kDa ‘companion’ auto-antigen of p62 overexpressed in cancer. Oncogene. 21:5006–5015. 2002.
9	Junttila MR, Puustinen P, Niemelä M, et al: CIP2A inhibits PP2A in human malignancies. Cell. 130:51–62. 2007. View Article : Google Scholar : PubMed/NCBI
10	Khanna A, Pimanda JE and Westermarck J: Cancerous inhibitor of protein phosphatase 2A, an emerging human oncoprotein and a potential cancer therapy target. Cancer Res. 73:6548–6553. 2013. View Article : Google Scholar : PubMed/NCBI
11	Boehm JS, Hession MT, Bulmer SE and Hahn WC: Transformation of human and murine fibroblasts without viral oncoproteins. Mol Cell Biol. 25:6464–6474. 2005. View Article : Google Scholar : PubMed/NCBI
12	Drayton S, Rowe J, Jones R, et al: Tumor suppressor p16^INK4adetermines sensitivity of human cells to transformation by cooperating cellular oncogenes. Cancer Cell. 4:301–310. 2003.
13	Westermarck J and Hahn WC: Multiple pathways regulated by the tumor suppressor PP2A in transformation. Trends Mol Med. 14:152–160. 2008. View Article : Google Scholar : PubMed/NCBI
14	Côme C, Laine A, Chanrion M, et al: CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 15:5092–5100. 2009.PubMed/NCBI
15	Dong QZ, Wang Y, Dong XJ, et al: CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol. 18:857–865. 2011. View Article : Google Scholar : PubMed/NCBI
16	Huang LP, Adelson ME, Mordechai E and Trama JP: CIP2A expression is elevated in cervical cancer. Cancer Biomark. 8:309–317. 2010.PubMed/NCBI
17	Vaarala MH, Väisänen MR and Ristimäki A: CIP2A expression is increased in prostate cancer. J Exp Clin Cancer Res. 29:1362010. View Article : Google Scholar : PubMed/NCBI
18	Chen KF, Liu CY, Lin YC, et al: CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells. Oncogene. 29:6257–6266. 2010. View Article : Google Scholar : PubMed/NCBI
19	Beckebaum S, Iacob S, Klein CG, et al: Assessment of allograft fibrosis by transient elastography and noninvasive biomarker scoring systems in liver transplant patients. Transplantation. 89:983–993. 2010. View Article : Google Scholar : PubMed/NCBI
20	Ren XS, Sato Y, Harada K, et al: Activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat. PLoS One. 9:e876602014. View Article : Google Scholar : PubMed/NCBI
21	Alayev A and Holz MK: mTOR signaling for biological control and cancer. J Cell Physiol. 228:1658–1664. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kim DH, Sarbassov DD, Ali SM, et al: mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 110:163–175. 2002. View Article : Google Scholar : PubMed/NCBI