An EGFR/Src-dependent ?4 integrin/FAK complex contributes to malignancy of breast cancer.

ABSTRACT: ?4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients, and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between ?4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of ?4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of ?4 integrin, which, in turn, recruits FAK to ?4 integrin and leads to FAK activation and signaling. Upon disruption of the ?4 integrin/FAK complex, tumorigenesis and metastasis in triple-negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of ?4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent ?4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer.

SUBMITTER: Tai YL 

PROVIDER: S-EPMC4637903 | biostudies-other | 2015

REPOSITORIES: biostudies-other