Research Papers:

Caveolin-1 Y14 phosphorylation suppresses tumor growth while promoting invasion

Bharat Joshi, Judy Pawling, Jay Shankar, Karina Pacholczyk, Yohan Kim, Wynn Tran, Fanrui Meng, Anas M. Abdel Rahman, Leonard J. Foster, Hon S. Leong, James W. Dennis and Ivan R. Nabi _

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Oncotarget. 2019; 10:6668-6677. https://doi.org/10.18632/oncotarget.27313

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Bharat Joshi1, Judy Pawling2, Jay Shankar1, Karina Pacholczyk2, Yohan Kim3, Wynn Tran1, Fanrui Meng1, Anas M. Abdel Rahman4, Leonard J. Foster5, Hon S. Leong3, James W. Dennis2 and Ivan R. Nabi1

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: [email protected]

Keywords: caveolin-1; TP53; tumor suppressor; tumor cell metabolism; invadopodia

Received: July 25, 2019     Accepted: October 26, 2019     Published: November 19, 2019


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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