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

• Published in: Oncotarget Vol. 8; no. 68; pp. 113034 - 113065
• Main Authors: Ogunbolude, Yetunde, Dai, Chenlu, Bagu, Edward T, Goel, Raghuveera Kumar, Miah, Sayem, MacAusland-Berg, Joshua, Ng, Chi Ying, Chibbar, Rajni, Napper, Scott, Raptis, Leda, Vizeacoumar, Frederick, Vizeacoumar, Franco, Bonham, Keith, Lukong, Kiven Erique
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 22.12.2017
• Subjects: Research Paper; triple negative breast cancer; breast cancer subtypes; basal A and B; STAT3; fyn-related kinase -FRK
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.22958

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 correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.