CREB‐binding protein regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathway. Issue 2 (5th November 2015)

• Record Type: Journal Article
• Authors: Tang, Zhipeng; Yu, Wendan; Zhang, Changlin; Zhao, Shilei; Yu, Zhenlong; Xiao, Xiangsheng; Tang, Ranran; Xuan, Yang; Yang, Wenjing; Hao, Jiaojiao; Xu, Tingting; Zhang, Qianyi; Huang, Wenlin; Deng, Wuguo; Guo, Wei
• Is Part Of: Molecular oncology. Volume 10:Issue 2(2016:Feb.)
• Page Start: 317
• Page End: 329
• Publication Date: 2015-11-05
• Subjects: CBP -- CPSF4 -- hTERT -- Lung cancer; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1016/j.molonc.2015.10.015
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : CBP (CREB‐binding protein) is a transcriptional co‐activator which possesses HAT (histone acetyltransferases) activity and participates in many biological processes, including embryonic development, growth control and homeostasis. However, its roles and the underlying mechanisms in the regulation of carcinogenesis and tumor development remain largely unknown. Here we investigated the molecular mechanisms and potential targets of CBP involved in tumor growth and survival in lung cancer cells. Elevated expression of CBP was detected in lung cancer cells and tumor tissues compared to the normal lung cells and tissues. Knockdown of CBP by siRNA or inhibition of its HAT activity using specific chemical inhibitor effectively suppressed cell proliferation, migration and colony formation and induced apoptosis in lung cancer cells by inhibiting MAPK and activating cytochrome C/caspase‐dependent signaling pathways. Co‐immunoprecipitation and immunofluorescence analyses revealed the co‐localization and interaction between CBP and CPSF4 (cleavage and polyadenylation specific factor 4) proteins in lung cancer cells. Knockdown of CPSF4 inhibited hTERT transcription and cell growth induced by CBP, and vice versa, demonstrating the synergetic effect of CBP and CPSF4 in the regulation of lung cancer cell growth and survival. Moreover, we found that high expression of both CBP and CPSF4 predicted a poor prognosis in the patients with lung adenocarcinomas. Collectively, our results indicate that CBP regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathways. Highlights: Knockdown of CBP or inhibition of its HAT activity inhibits lung cancer cell growth and induces apoptosis. Knockdown of CBP or inhibition of its HAT activity inactivates MAPK signaling pathway. CBP interacts with and acetylates CPSF4 to promote hTERT expression and tumor growth in lung cancer cells. Overexpression of both CBP and CPSF4 predicted poor prognosis of the patients with lung adenocarcinomas.