Open AccessFRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition
Author(s) -
Yetunde Ogunbolude,
Chenlu Dai,
Edward T. Bagu,
Raghuveera Kumar Goel,
Sayem Miah,
Joshua MacAusland-Berg,
Chi Ying Ng,
Rajni Chibbar,
Scott Napper,
Leda Raptis,
Frederick S. Vizeacoumar,
Franco J. Vizeacoumar,
Keith Bonham,
Kiven Lukong
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.22958
Subject(s) - epithelial–mesenchymal transition , cancer research , biology , kinome , cell growth , cell migration , signal transduction , vimentin , mesenchymal stem cell , microbiology and biotechnology , cell culture , downregulation and upregulation , immunology , gene , biochemistry , genetics , immunohistochemistry
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.