Oncotarget

Research Papers:

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

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 Vizeacoumar, Franco Vizeacoumar, Keith Bonham and Kiven Erique Lukong _

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Oncotarget. 2017; 8:113034-113065. https://doi.org/10.18632/oncotarget.22958

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Abstract

Yetunde Ogunbolude1, Chenlu Dai1, Edward T. Bagu1,2, Raghuveera Kumar Goel1, Sayem Miah1,4, Joshua MacAusland-Berg1, Chi Ying Ng1, Rajni Chibbar3, Scott Napper1,5, Leda Raptis6, Frederick Vizeacoumar2, Franco Vizeacoumar2, Keith Bonham1,2 and Kiven Erique Lukong1

1Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada

2Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, and Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Canada

3Department of Pathology Royal University Hospital Saskatchewan, Saskatoon, Canada

4Departments of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, MO, USA

5Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada

6Departments of Microbiology and Immunology and Pathology, Queen’s University, Kingston, Canada

Correspondence to:

Kiven Erique Lukong, email: Kiven.lukong@usask.ca

Keywords: fyn-related kinase -FRK; breast cancer subtypes; triple negative breast cancer; basal A and B; STAT3

Received: May 30, 2017    Accepted: November 16, 2017    Published: December 06, 2017

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 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.


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