TSPAN7 Functions as an Antitumor Agent Through the STK11/AMPK/mTOR Axis in Colorectal Cancer

Abstract

Background: Tetraspanin 7 (TSPAN7), a quadruple transmembrane glycoprotein, is involved in the growth, development, and energy metabolism of cells, particularly in tumor cells. Despite its recognized significance, the role of TSPAN7 in colorectal cancer (CRC) remains unexplored. The purpose of this study is to explore the antitumor activity of TSPAN7 through the STK11/AMPK/mTOR pathway. Methods: Analysis of differential genes in normal colon and CRC tissues was conducted using the Gene Expression Omnibus (GEO) database. Ten potential genes, including TSPAN7, were also identified through the database screening. Results: Assessment of TSPAN7 alterations in both CRC tissues as well as cell lines revealed reduced expression as compared to normal colon tissues. Based on the findings, modulation of TSPAN7 expression was performed through overexpression and downregulation in vitro within CRC cells. The findings indicated that TSPAN7 exerted a negative regulatory influence on the migration and proliferation of CRC cells. An examination of AMPK and mTOR phosphorylation levels revealed that TSPAN7 affected the phosphorylation of these proteins via STK11. Conclusion: In CRC, TSPAN7 exerts antitumor effects through the STK11/AMPK/mTOR axis.

Keywords: AMPK/mTOR; STK11; TSPAN7; cell proliferation; colorectal cancer (CRC).