Receptor-type protein tyrosine phosphatase alpha (PTP alpha) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion
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 previo...
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Veröffentlicht in: | Molecular biology of the cell 2021-04, Vol.32 (7), p.567-578 |
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Zusammenfassung: | 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 (PTP alpha) regulates focal adhesion formation and migration of normal cells. Here we report a novel role for PTP alpha in promoting triple-negative breast cancer cell invasion in vitro and in vivo. We show that PTP alpha knockdown reduces ECM degradation and cellular invasion of MDA-MB-231 cells through Matrigel. PTP alpha is not a component of TKS5-positive structures resembling invadopodia; rather, PTP alpha localizes with endosomal structures positive for MMP14, caveolin-1, and early endosome antigen 1. Furthermore, PTP alpha regulates MMP14 localization to plasma membrane protrusions, suggesting a role for PTP alpha in intracellular trafficking of MMP14. Importantly, we show that orthotopic MDA-MB-231 tumors depleted in PTP alpha exhibit reduced invasion into the surrounding mammary fat pad. These findings suggest a novel role for PTP alpha in regulating the invasion of triple-negative breast cancer cells. |
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ISSN: | 1059-1524 1939-4586 |
DOI: | 10.1091/mbc.E20-01-0060 |