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.

• Authors: Hui Bai, Chenchen Wang, Yu Qi, Jin Xu, Nan Li, Lili Chen, Bin Jiang, Xudong Zhu, Hanwen Zhang, Xiaoyu Li, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, Qi Chen
• Journal: BMC cancer (BMC Cancer) Vol. 19 Issue 1 Pg. 454 (May 15 2019) ISSN: 1471-2407 [Electronic] England
• PMID: 31092229 (Publication Type: Journal Article)

Chemical References

• STAT3 Transcription Factor
• STAT3 protein, human
• Vault Ribonucleoprotein Particles
• major vault protein

Topics

• Aged
• Animals
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Cell Proliferation
• Cell Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Mice
• Middle Aged
• Neoplasm Transplantation
• Phosphorylation
• Prognosis
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Survival Analysis
• Up-Regulation
• Vault Ribonucleoprotein Particles (genetics, metabolism)