Receptor-type protein tyrosine phosphatase alpha (PTPα) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion.

Autor: Decotret LR; Integrative Oncology, BC Cancer, Vancouver, British Columbia, BC V5Z 4E6, Canada.; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, BC V5Z 4H4, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada., Wadsworth BJ; Integrative Oncology, BC Cancer, Vancouver, British Columbia, BC V5Z 4E6, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada., Li LV; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, BC V5Z 4H4, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada., Lim CJ; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, BC V5Z 4H4, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada.; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada., Bennewith KL; Integrative Oncology, BC Cancer, Vancouver, British Columbia, BC V5Z 4E6, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada., Pallen CJ; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, BC V5Z 4H4, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada.; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, BC V6H 3V4, Canada.
Jazyk: angličtina
Zdroj: Molecular biology of the cell [Mol Biol Cell] 2021 Apr 01; Vol. 32 (7), pp. 567-578. Date of Electronic Publication: 2021 Feb 10.
DOI: 10.1091/mbc.E20-01-0060
Abstrakt: The ability of cancer cells to invade surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membranes of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that the protein tyrosine phosphatase alpha (PTPα) regulates focal adhesion formation and migration of normal cells. Here we report a novel role for PTPα in promoting triple-negative breast cancer cell invasion in vitro and in vivo. We show that PTPα knockdown reduces ECM degradation and cellular invasion of MDA-MB-231 cells through Matrigel. PTPα is not a component of TKS5-positive structures resembling invadopodia; rather, PTPα localizes with endosomal structures positive for MMP14, caveolin-1, and early endosome antigen 1. Furthermore, PTPα regulates MMP14 localization to plasma membrane protrusions, suggesting a role for PTPα in intracellular trafficking of MMP14. Importantly, we show that orthotopic MDA-MB-231 tumors depleted in PTPα exhibit reduced invasion into the surrounding mammary fat pad. These findings suggest a novel role for PTPα in regulating the invasion of triple-negative breast cancer cells.
Databáze: MEDLINE
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