Caveolin-1 Y14 phosphorylation suppresses tumor growth while promoting invasion
Why this work is in the frame
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Bibliographic record
Abstract
// Bharat Joshi 1 , Judy Pawling 2 , Jay Shankar 1 , Karina Pacholczyk 2 , Yohan Kim 3 , Wynn Tran 1 , Fanrui Meng 1 , Anas M. Abdel Rahman 4 , Leonard J. Foster 5 , Hon S. Leong 3 , James W. Dennis 2 and Ivan R. Nabi 1 1 Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Department of Molecular Genetics, University of Toronto, Toronto, Canada 3 Translational Prostate Cancer Research Group, London Regional Cancer Program, University of Western Ontario, London, Canada 4 Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia 5 Centre for High-throughput Biology, University of British Columbia, Vancouver, Canada Correspondence to: Ivan R. Nabi, email: irnabi@mail.ubc.ca Keywords: caveolin-1; TP53; tumor suppressor; tumor cell metabolism; invadopodia Received: July 25, 2019     Accepted: October 26, 2019     Published: November 19, 2019 ABSTRACT Caveolin-1 is a transmembrane protein with both tumor promoter and suppressor functions that remain poorly understood. Cav1 phosphorylation by Src kinase on tyrosine 14 is closely associated with focal adhesion dynamics and tumor cell migration, however the role of pCav1 in vivo in tumor progression remains poorly characterized. Herein, we expressed phosphomimetic Y14D, wild type, and non-phosphorylatable Y14F forms of Cav1 in MDA-MB-435 cancer cells. Expression of Cav1Y14D reduced cell proliferation and induced the TP53 tumor suppressor. Ectopic expression in MDA-MB-435 cells of Y14 phosphorylatable Cav1 was required for induction of TP53 in response to oxidative stress. Cav1Y14D promotes an apparent reversal of the Warburg effect and markedly inhibited tumor growth in vivo . However, Cav1 induced pseudopodial recruitment of glycolytic enzymes, and time-lapse intravital imaging showed increased invadopodia protrusion and extravasation into blood vessels for Cav1WT and Y14D but not for Y14F. Our results suggest that Cav1 Y14 phosphorylation levels play a role in the conflicting demands on metabolic resources associated with cancer cell proliferation versus motility.
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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) | 0.000 | 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 it