CIP2A overexpression up-regulates Akt signaling pathway in metastasis breast cancer cell

Research Article
American Journal of BioMedicine Volume 3, Issue 10, pages 658-673
Published: October 27, 2015

Chen Hsua, b, James H. Woodgetta, Tsung-Han Huanga, b, Trevor Penga, c, Patrick Wagnera, Gabriel Tyritzisa, John Shimizuamail of corresponding author


Breast cancer, a major worldwide health threat, is considered to comprise a group of biologically heterogeneous diseases. Protein phosphatase-2A(PP2A) functions as a serine/threonine phosphatase and has been shown to regulate the activity of several oncogenic proteins, and loss of PP2A function has been identified in several malignancies. Recently, an emerging human oncoprotein, cancerous inhibitor of PP2A (CIP2A) has been shown to inhibit PP2A activity. In this study, we investigate the effect and mechanism of CIP2A in metastesis breast cancer cells. We found that CIP2A upregulated phospho-Akt (p-Akt) correlated with metastesis breast cancer cells. Moreover, silencing CIP2A by small interfering RNA (siRNA) induced apoptosis of metastesis breast cancer cell.

Keywords: Breast cancer; CIP2A; Metastesis; Akt; PP2A

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.



1. Eccles SA, Aboagye EO, Ali S, et al. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Res 2013; 15:R92. [PubMed]

2. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74:2913–2921. [PubMed]

3. Tryggvadottir L, Sigvaldason H, Olafsdottir GH, et al. Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920–2000. J Natl Cancer Inst 2006; 98:116–122. [PubMed]

4. Parkin DM, Boyd L, Walker LC. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer 2011; 105:S77–S81. [PubMed]

5. Brooks JD. Translational genomics. The challenge of developing cancer biomarkers. Genome Res 2012; 22:183-187. [PubMed]

6. Soo Hoo L, Zhang JY, Chan EK. Cloning and characterization of a novel 90 kDa ‘companion’ auto-antigen of p62 overexpressed in cancer. Oncogene 2002; 21:5006-5015. [PubMed]

7. Amir E, Freedman OC, Seruga B, Evans DG. Assessing women at high risk of breast cancer: a review of risk assessment models. J Natl Cancer Inst 2010; 102:680–691. [PubMed]

8. Schonfeld SJ, Pee D, Greenlee RT, et al. Effect of changing breast cancer incidence rates on the calibration of the Gail model. J Clin Oncol 2010; 28:2411–2417. [PubMed]

9. Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Ann Intern Med 2008; 148:337–347. [PubMed]

10. Lucas CM, Harris RJ, Giannoudis A, Copland M, Slupsky JR, Clarke RE. Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood 2011; 117:6660–8.

11.Teng HW, Yang SH, Lin JK, et al. CIP2A is a predictor of poor prognosis in colon cancer. J Gastrointest Surg 2012; 16:1037–4.

12. Vaarala MH, Vaisanen MR, Ristimaki A. CIP2A expression is increased in prostate cancer. J Exp Clin Cancer Res 2010; 29:136. [PubMed]

13. Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ. The quantitative analysis of mammographic densities. Phys Med Biol 1994; 39:1629–1638. [PubMed]

14. Ren J, Li W, Yan L, et al. Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients’ survival. Br J Cancer 2011; 105:1905–11.

15. Teng HW, Yang SH, Lin JK, et al. CIP2A is a predictor of poor prognosis in colon cancer. J Gastrointest Surg 2012; 16:1037–47.

16. Vaarala MH, Vaisanen MR, Ristimaki A. CIP2A expression is increased in prostate cancer. J Exp Clin Cancer Res 2010; 29:136. [PubMed]

17. Junttila MR, Puustinen P, Niemela M, et al. CIP2A inhibits PP2A in human malignancies. Cell 2007; 130:51–62.

18. Tan EM. Antinuclear antibodies. Diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 1989; 44:93-151. [PubMed]

19. Huang CY, Wei CC, Chen KC, et al. Bortezomib enhances radiation-induced apoptosis in solid tumors by inhibiting CIP2A. Cancer Lett 2012; 317:9-15. [PubMed]

20. Perrotti D, Neviani P. PP2A: a target for anticancer therapy. Lancet Oncol 2013, 14:e229-e238. [PubMed]

21. Eichhorn PJ, Creyghton MP, Bernards R. PP2A regulatory subunits and cancer. Biochim Biophys Acta 2009; 1795(1):1–15. [PubMed]

22. Perrotti D, Neviani P. Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias. Cancer Metastasis Rev 2008; 27(2):159–68. [PubMed]

23. Samanta AK, Chakraborty SN, Wang Y, et al. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene 2009; 28(14):1669–81. [PubMed]

24. McCright B, Virshup DM. Identification of a new family of protein phosphatase 2A regulatory subunits. J Biol Chem 1995; 270(44):26123–8. [PubMed]

25. Sablina AA, Hector M, Colpaert N, Hahn WC. Identification of PP2A complexes and pathways involved in cell transformation. Cancer Res 2010; 70(24):10474–84. [PubMed]

26. Tsatsanis C, Spandidos DA. The role of oncogenic kinases in human cancer (Review). Int J Mol Med 2000; 5(6):583–90. [PubMed]

27. Neuzil J, Weber T, Schroder A, et al. Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements. Faseb J 2001; 15(2):403–15. [PubMed]

28. Kar S, Palit S, Ball WB, Das PK. Carnosic acid modulates Akt/IKK/NF-kappaB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis 2012; 17(7):735–47. [PubMed]

29. Kim SW, Kim HJ, Chun YJ, Kim MY. Ceramide produces apoptosis through induction of p27(kip1) by protein phosphatase 2A-dependent Akt dephosphorylation in PC-3 prostate cancer cells. J Toxicol Environ Health A 2010; 73(21–22):1465–76. [PubMed]

30. Sebestyen A, Hajdu M, Kis L, Barna G, Kopper L. Smad4-independent, PP2A-dependent apoptotic effect of exogenous transforming growth factor beta 1 in lymphoma cells. Exp Cell Res. 2007;313(15):3167–74. [PubMed]

Limited access article

limited access This article with limited access need to be buy, before continue with your purchase please read carefully the AJBM terms and conditions of purchase.

Purchase this article at rate $55.00 and received Full-Text/PDF
You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use. Use the coding below to purchase your article as PDF by credit card, debit card, payball will be asked to supply your billing card information.


For any technique error please contact us and will be response to sending purchase article by email.

Thank you for visiting American Journal of BioMedicine.  * = Required fields

[gravityform id=”6″ name=”Feedback”]

Print Friendly, PDF & Email