Abstract
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.
Highlights
Cancerous inhibitor of phosphatase 2A (PP2A) (CIP2A) is a recently characterized oncoprotein, which promotes cancer cell proliferation
Our studies showed that Cancerous inhibitor of PP2A (CIP2A) positively regulates the phosphorylation of AKT, p38 kinase and c-Jun activated kinase (JNK)
CIP2A elicits autoimmune response in lung cancer patients To identify novel tumor-associated antigens in lung cancer patients, we screened the presence of autoantibodies
Summary
Cancerous inhibitor of PP2A (CIP2A) is a recently characterized oncoprotein, which promotes cancer cell proliferation. The role of CIP2A in lung cancer progression is still not well understood. The 5 year survival rate of lung cancer is as low as 15 % [1]. The disease-associated symptoms imposed a challenging situation for early cancer diagnosis. Those symptoms can be hardly felt by the patients themselves until the disease is progressed to an advanced stage, which makes lung cancer diagnosed at a late stage when the cancer cells have metastasized [2]. Chest x-ray check and spiral CT scans have been used in routine screening of lung cancer, they are ineffective methods with insufficient accuracy due to the limited technology capabilities, observer variations and data interpretations. The development of reliable biomarkers for early detection of lung cancer is an urgent field since there is no currently approved screening test for lung cancer detection
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