J Cancer 2018; 9(16):2825-2833. doi:10.7150/jca.25993

Research Paper

Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β

Shuanshuan Xie1, Yang Liu1, Xuan Li1, Min Tan1, Changhui Wang1✉, Jeffrey Field2, Guo-Lei Zhou3

1. Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
2. Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
3. Department of Biological Sciences, Arkansas State University, State University, AR 72467, USA.

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Xie S, Liu Y, Li X, Tan M, Wang C, Field J, Zhou GL. Phosphorylation of the Cytoskeletal Protein CAP1 Regulates Non-Small Cell Lung Cancer Survival and Proliferation by GSK3β. J Cancer 2018; 9(16):2825-2833. doi:10.7150/jca.25993. Available from http://www.jcancer.org/v09p2825.htm

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Adenylate cyclase-associated protein 1 (CAP1) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that knockdown of CAP1 inhibited cell proliferation and induced apoptosis in vitro and in vivo. Moreover, phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and the proliferation in CAP1-knockdown cells and GSK3β kinase inhibitor LiCl inhibited cell phosphorylation site S307/S309 by up-regulating the expression of p53, BAK, BAD and cleaved PARP induced ROS production, decreased lung cancer cell viability, adhesion, proliferation, migration and invasion, and induction of apoptosis. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of lung cancer, tailored for specific types of the highly diverse disease.

Keywords: Adenylate cyclase-associated protein, Kinase, Phosphorylation, Lung cancer