FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition
Bibliographic record
Abstract
// Yetunde Ogunbolude 1 , Chenlu Dai 1 , Edward T. Bagu 1, 2 , Raghuveera Kumar Goel 1 , Sayem Miah 1, 4 , Joshua MacAusland-Berg 1 , Chi Ying Ng 1 , Rajni Chibbar 3 , Scott Napper 1, 5 , Leda Raptis 6 , Frederick Vizeacoumar 2 , Franco Vizeacoumar 2 , Keith Bonham 1, 2 and Kiven Erique Lukong 1 1 Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada 2 Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, and Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Canada 3 Department of Pathology Royal University Hospital Saskatchewan, Saskatoon, Canada 4 Departments of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, MO, USA 5 Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada 6 Departments 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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".