CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer

BMC Cancer

Research Article

Xinxin Liu¹  Bo Peng¹  Yurong Chai¹  Yang Li¹  Jianying Zhang¹ 

[1] Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, 79968, El Paso, TX, USA;

关键词: Tumor-associated antigen;    Cancerous inhibitor of PP2A;    c-Jun activated kinase (JNK);    Mitogen activated kinase 4 (MKK4);    Cell proliferation;   

DOI  :  10.1186/s12885-015-1899-0

 received in 2014-10-03, accepted in 2015-11-03,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCancerous inhibitor of PP2A (CIP2A) is a recently characterized oncoprotein, which promotes cancer cell proliferation. But the role of CIP2A in lung cancer progression is still not well understood.MethodsThe expression level of CIP2A in lung cancer tissues was examined by immunohistochemistry. CIP2A-associated cell proliferation was performed by knock down or overexpression of CIP2A in lung cancer cells. Phospho-array was used to screen kinase candidates related to expression change of CIP2A. Western-blot and luciferase reporter assay were used to validate phospho-array results.ResultsOverexpression of CIP2A in lung cancer not only triggers immune response in lung cancer patients but also promotes lung cancer cell proliferation. By phospho-array, several kinase candidates were identified, one of which is c-Jun activated kinases (JNK). The knock down of CIP2A decreased JNK phosphorylation, and the phosphorylation of downstream transcriptional factors, ATF2 and c-Jun, whose transcriptional activity were decreased as well. Furthermore, the expression level of CIP2A also affected the phosphorylation of the upstream kinase of JNK, MKK4/MKK7. At last, treatment with JNK inhibitor partially abolished CIP2A-induced cell proliferation.ConclusionCIP2A is a tumor-associated autoantigen in lung cancer, which promote lung cancer proliferation partially through MKK4/7-JNK signaling pathway.

【 授权许可】

CC BY   
© Peng et al. 2015