A trafficking regulatory subnetwork governs α_Vβ₆ integrin-HER2 cross-talk to control breast cancer invasion and drug resistance.

ABSTRACT: HER2 and α_Vβ₆ integrin are independent predictors of breast cancer survival and metastasis. We identify an α_Vβ₆/HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound α_Vβ₆ recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2). The RAB5/RAB7A/GDI2 functional module mediates direct cross-talk between α_Vβ₆ and HER2, affecting receptor trafficking and signaling. Acute exposure to trastuzumab increases recruitment of the subnetwork to α_Vβ₆, but trastuzumab resistance decouples GDI

SUBMITTER: Maldonado H 

PROVIDER: S-EPMC11616693 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature