FRK suppresses human glioma growth by inhibiting ITGB1/FAK signaling

Fyn-related kinase (FRK), a member of the Src-related tyrosine kinase family, functions as a tumor suppressor in several malignancies. We previously showed that FRK overexpression inhibited the growth of glioma cells. However, it is unknown whether FRK is equally effective against intracranial glioma in vivo, and the mechanism by which FRK influences glioma cell growth remains unclear. In this study, we found that tumor volume was reduced by about one-third in mice with FRK overexpression, which showed improved survival relative to controls. Immunofluorescence analysis revealed that FRK overexpression inhibited glioma cell proliferation and induced their apoptosis. Importantly, in vitro we further found that FRK decreased the expression of integrin subunit β1 (ITGB1) at both the mRNA and protein levels. FRK also inhibited transactivation by ITGB1, resulting in the suppression of its target proteins AKT and focal adhesion kinase (FAK). ITGB1 overexpression promoted glioma cell growth and partially reduced FRK-induced growth suppression. These results indicate that FRK inhibits human glioma growth via regulating ITGB1/FAK signaling and provide a potential therapeutic target for the treatment of glioma. •FRK overexpression inhibits intracranial glioma cell growth in vivo.•FRK overexpression inhibits intracranial glioma cell proliferation and apoptosis in vivo.•Intracranial glioma invasiveness and angiogenesis are unaffected by FRK overexpression in vivo.•FRK overexpression alters the expression of ITGB1 and its downstream targets in vitro.•Restoration of ITGB1 expression abrogates FRK-repressed glioma cell growth in vitro.