Integrin β5 interacts with G3BP1 through activating FAK/Src signaling pathway to promote gastric carcinogenesis.

Previous studies demonstrated that integrin β5 (ITGB5) play an important role in the occurrence and development of various malignant tumors. However, its functional mechanism in gastric cancer (GC) remains obscure. We detected that ITGB5 was overexpressed in GC tissues and its high-level expression was associated with poor survival and advanced stages. Functional assays indicated that overexpression of ITGB5 promotes the proliferation, migration and invasion of GC cells in both vitro and vivo. Mechanistically, we observed a lower variability and invasiveness when GC cells were treated with Defactinib and Saractinib, indicating that activated FAK-Src signaling may lead to an aggressive GC process. Then, we reveal that knockdown of ITGB5 reduces phosphorylation of FAK and Src, without changing total FAK/Src levels. Additionally, ITGB5 interacts with G3BP1 and increases the phosphorylation of FAK and Src. This leads to activation of FAK/Src signaling, which are critical regulators of GC development. Our findings uncover a previously unrecognized mechanism of the ITGB5/G3BP1/FAK/Src axis involved in GC development and the oncogenic potential of ITGB5 in GC, thus providing a potential therapeutic target for advanced GC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-14067-z.