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Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression

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Abstract

Caveolin-1 (CAV1) has long been implicated in cancer progression, and while widely accepted as an oncogenic protein, CAV1 also has tumor suppressor activity. CAV1 was first identified in an early study as the primary substrate of Src kinase, a potent oncoprotein, where its phosphorylation correlated with cellular transformation. Indeed, CAV1 phosphorylation on tyrosine-14 (Y14; pCAV1) has been associated with several cancer-associated processes such as focal adhesion dynamics, tumor cell migration and invasion, growth suppression, cancer cell metabolism, and mechanical and oxidative stress. Despite this, a clear understanding of the role of Y14-phosphorylated pCAV1 in cancer progression has not been thoroughly established. Here, we provide an overview of the role of Src-dependent phosphorylation of tumor cell CAV1 in cancer progression, focusing on pCAV1 in tumor cell migration, focal adhesion signaling and metabolism, and in the cancer cell response to stress pathways characteristic of the tumor microenvironment. We also discuss a model for Y14 phosphorylation regulation of CAV1 effector protein interactions via the caveolin scaffolding domain.

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Funding

Work on CAV1 in the Nabi lab is supported by grants from the Canadian Institutes for Health Research (CIHR PJT-156424, PJT-159845). Timothy Wong is supported by British Columbia Graduate Scholarship #6768 and UBC Faculty of Medicine Graduate Award #6442, Fiona Dickson by UBC Faculty of Medicine Graduate Award #6442 and NSERC Canada Graduate Scholarship Master’s Award #6563, and Logan Timmins by British Columbia Graduate Scholarship #6768.

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  1. Timothy H. Wong and Fiona H. Dickson contributed equally to this work.

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  1. Life Sciences Institute, Department of Cellular and Physiological Sciences, School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada

    Timothy H. Wong, Fiona H. Dickson, Logan R. Timmins & Ivan R. Nabi

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Wong, T.H., Dickson, F.H., Timmins, L.R. et al. Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression. Cancer Metastasis Rev 39, 455–469 (2020). https://doi.org/10.1007/s10555-020-09892-9

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