Major vault protein suppresses lung cancer cell proliferation by inhibiting STAT3 signaling pathway

BMC Cancer

Jin Xu¹  Yu Qi²  Yong Xu²  Hui Bai²  Xiaoyu Li²  Qing Yang²  Junqing Ma²  Qi Chen²  Lili Chen²  Hanwen Zhang²  Jingjing Ben²  Chenchen Wang²  Xudong Zhu²  Bin Jiang²  Nan Li³ 

[1] 0000 0000 9255 8984, grid.89957.3a, Department of Molecular Cell Biology and Toxicology, Key Laboratory of Modern Toxicology, Nanjing Medical University, Nanjing, China;0000 0000 9255 8984, grid.89957.3a, Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China;0000 0000 9255 8984, grid.89957.3a, Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China;Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, China;

关键词: Non-small cell lung cancer;    Major vault protein;    STAT3;    Cell proliferation;    Cell apoptosis;   

DOI  :  10.1186/s12885-019-5665-6

来源: publisher

【 摘 要 】

BackgroundMajor vault protein (MVP) is the major component of vault, a eukaryotic organelle involved in multiple cellular processes, and is important in multiple cellular processes and diseases including the drug resistance in cancer chemotherapies. However, the role of MVP in lung cancer remains unclear.MethodsWe examined MVP expression in 120 non-small cell lung cancer (NSCLC) tumors and matched normal tissues by immunohistochemistry. Its relationship with NSCLC prognosis was determined by investigating the patient cohort and analyzing the data from a published dataset consisting with more than 1900 lung cancer patients. We further performed shRNA-introduced knockdown of MVP in Lewis lung carcinoma (LLC) cells and examined its effects on the tumor formation in a xenograft mouse model and the tumor cell proliferation, apoptosis, and signal transduction in vitro.ResultsWe found that MVP was up-regulated significantly in tumor tissues compared with the matched tumor-adjacent normal tissues. The increased expression of MVP in lung adenocarcinoma was associated with a better prognosis. Knockdown of MVP in LLC cells promoted xenografted lung cancer formation in mice, which was accompanied with accelerated tumor cell proliferation and suppressed cell apoptosis in vitro. Knockdown of MVP stimulated STAT3 phosphorylation, nuclear localization, and activation of JAK2 and RAF/MEK/ERK pathways in LLC cells. Administration of STAT3 inhibitor WP1066 could prevent MVP knockdown induced tumorigenesis.ConclusionsOur findings demonstrate that MVP may act as a lung tumor suppressor via inhibiting STAT3 pathway. MVP would be a potential target for novel therapies of lung adenocarcinoma.

【 授权许可】

CC BY