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Open Access 01-12-2020 | Gastric Cancer | Primary research

TSPAN9 suppresses the chemosensitivity of gastric cancer to 5-fluorouracil by promoting autophagy

Authors: Yaoyue Qi, Weiwei Qi, Shihai Liu, Libin Sun, Aiping Ding, Guohong Yu, Hui Li, Yixuan Wang, Wensheng Qiu, Jing Lv

Published in: Cancer Cell International | Issue 1/2020

Abstract

Background

The issue of drug resistance in gastric cancer has attracted global attention. TSPAN9, a 4-transmembrane protein that plays an important role in tumor progression and signal transduction, has been found to be closely related to tumor invasion, metastasis, and autophagy.

Methods

Immunoblotting was used to evaluate TSPAN9 expression in parental and drug-resistant gastric cancer cells. Functional assays, such as the CCK-8 assay, were used to detect the proliferation of gastric cancer cells and the response of TSPAN9 to 5-fluorouracil (5-FU). Western blotting was used to analyze the expression of constituents of the PI3K/AKT/mTOR-mediated autophagy pathway induced by TSPAN9. Coimmunoprecipitation was performed to assess the specific mechanism by which TSPAN9 affects the PI3K pathway.

Results

We demonstrated that TSPAN9 is overexpressed in 5-FU-resistant cells compared to parental cells. 5-FU-mediated inhibition of cell proliferation can be significantly restored by increasing TSPAN9 expression, and inhibiting this expression in drug-resistant cells can restore the sensitivity of the cells to 5-FU. In addition, TSPAN9 also significantly promoted autophagy in gastric cancer cells in vitro. Further studies indicated that TSPAN9 downregulates the expression of PI3K and proteins associated with PI3K-mediated autophagy. In addition, TSPAN9 interacts with PI3K and inhibits its catalytic activity.

Conclusion

The current study reveals the important role of TSPAN9 in drug resistance to 5-FU in gastric cancer. It also provides a new target to clinically address drug-resistant gastric cancer and will contribute to the treatment strategy of this disease.

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Title: TSPAN9 suppresses the chemosensitivity of gastric cancer to 5-fluorouracil by promoting autophagy
Authors: Yaoyue Qi
Weiwei Qi
Shihai Liu
Libin Sun
Aiping Ding
Guohong Yu
Hui Li
Yixuan Wang
Wensheng Qiu
Jing Lv
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Gastric Cancer
Gastric Cancer
Published in: Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-019-1089-2

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