Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth
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  • 作者:Na Liu ; Qing-Mei He ; Jie-Wei Chen ; Ying-Qin Li ; Ya-Fei Xu ; Xian-Yue Ren…
  • 关键词:Nasopharyngeal carcinoma ; CIP2A ; Proliferation ; Cell growth ; Survival
  • 刊名:Molecular Cancer
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:13
  • 期:1
  • 全文大小:1,035 KB
  • 参考文献:1. Xu, ZJ, Zheng, RS, Zhang, SW, Zou, XN, Chen, WQ (2013) Nasopharyngeal carcinoma incidence and mortality in China in 2009. Chin J Cancer 32: pp. 453-460 CrossRef
    2. Cho, WC (2010) Most common cancers in Asia-Pacific region: nasopharyngeal carcinoma. Cancer report of Asian-Pacific region 2010. pp. 284-289
    3. Jemal, A, Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D (2011) Global cancer statistics. CA Cancer J Clin 61: pp. 69-90 CrossRef
    4. Lai, SZ, Li, WF, Chen, L, Luo, W, Chen, YY, Liu, LZ, Sun, Y, Lin, AH, Liu, MZ, Ma, J (2011) How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?. Int J Radiat Oncol Biol Phys 80: pp. 661-668 CrossRef
    5. Chen, Y, Sun, Y, Liang, SB, Zong, JF, Li, WF, Chen, M, Chen, L, Mao, YP, Tang, LL, Guo, Y, Lin, AH, Liu, MZ, Ma, J (2013) Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China. Cancer 119: pp. 2230-2238 CrossRef
    6. Junttila, MR, Puustinen, P, Niemel?, M, Ahola, R, Arnold, H, B?ttzauw, T, Ala-aho, R, Nielsen, C, Ivaska, J, Taya, Y, Lu, SL, Lin, S, Chan, EK, Wang, XJ, Grènman, R, Kast, J, Kallunki, T, Sears, R, K?h?ri, VM, Westermarck, J (2007) CIP2A inhibits PP2A in human malignancies. Cell 130: pp. 51-62 CrossRef
    7. Khanna, A, B?ckelman, C, Hemmes, A, Junttila, MR, Wiksten, JP, Lundin, M, Junnila, S, Murphy, DJ, Evan, GI, Haglund, C, Westermarck, J, Ristim?ki, A (2009) MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst 101: pp. 793-805 CrossRef
    8. Niemel?, M, Kauko, O, Sihto, H, Mpindi, JP, Nicorici, D, Pernil?, P, Kallioniemi, OP, Joensuu, H, Hautaniemi, S, Westermarck, J (2012) CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes. Oncogene 31: pp. 4266-4278 CrossRef
    9. C?me, C, Laine, A, Chanrion, M, Edgren, H, Mattila, E, Liu, X, Jonkers, J, Ivaska, J, Isola, J, Darbon, JM, Kallioniemi, O, Thézenas, S, Westermarck, J (2008) CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res 15: pp. 5092-5100 CrossRef
    10. Li, W, Ge, Z, Liu, C, Liu, Z, Bj?rkholm, M, Jia, J, Xu, D (2008) CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res 14: pp. 3722-3728 CrossRef
    11. Puustinen, P, Rytter, A, Mortensen, M, Kohonen, P, Moreira, JM, J??ttel?, M (2014) CIP2A oncoprotein controls cell growth and autophagy through TORC1 activation. J Cell Biol 204: pp. 713-727 CrossRef
    12. Dong, QZ, Wang, Y, Dong, XJ, Li, ZX, Tang, ZP, Cui, QZ, Wang, EH (2011) CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol 18: pp. 857-865 CrossRef
    13. Wiegering, A, Pfann, C, Uthe, FW, Otto, C, Rycak, L, M?der, U, Gasser, M, Waaga-Gasser, AM, Eilers, M, Germer, CT (2013) CIP2A influences survival in colon cancer and is critical in maintaining Myc expression. PLoS One 8: pp. e75292 CrossRef
    14. Yu, G, Liu, G, Dong, J, Jin, Y (2013) Clinical implications of CIP2A protein expression in breast cancer. Med Oncol 30: pp. 524 Cros
  • 刊物主题:Cancer Research; Oncology;
  • 出版者:BioMed Central
  • ISSN:1476-4598
文摘
Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. Results CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P--.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P--.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P--.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. Conclusions Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC.

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