FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition. Oncotarget. 2017 Dec 22;8(68):113034-113065 Authors: Ogunbolude Y, Dai C, Bagu ET, Goel RK, Miah S, MacAusland-Berg J, Ng CY, Chibbar R, Napper S, Raptis L, Vizeacoumar F, Vizeacoumar F, Bonham K, Lukong KE Abstract The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correl...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research