Dataset Information

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

ABSTRACT:

Background

Major 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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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.

SUBMITTER: Bai H

PROVIDER: S-EPMC6521381 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Bai Hui H Wang Chenchen C Qi Yu Y Xu Jin J Li Nan N Chen Lili L Jiang Bin B Zhu Xudong X Zhang Hanwen H Li Xiaoyu X Yang Qing Q Ma Junqing J Xu Yong Y Ben Jingjing J Chen Qi Q

BMC cancer 20190515 1

<h4>Background</h4>Major 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.<h4>Methods</h4>We examined MVP expression in 120 non-small cell lung cancer (NSCLC) tumors and matched normal tissues by immunohistochemistry. Its relationship with NSCLC prognosis was ...[more]

PMID: 31092229

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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