The ability of cancer cells to invade into surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membrane of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that 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 tumours depleted of 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.

癌细胞侵入周围组织的能力需要细胞外基质 (ECM) 的降解。侵袭性结构，如侵袭伪足，在癌细胞的质膜上形成并分泌 ECM 降解蛋白酶，在癌细胞侵袭中起关键作用。我们之前已经表明蛋白酪氨酸磷酸酶 α (PTPα) 调节正常细胞的粘着斑形成和迁移。在这里，我们报告了 PTPα在体外和体内促进三阴性乳腺癌细胞侵袭的新作用. 我们表明 PTPα 敲低通过基质胶减少了 ECM 降解和 MDA-MB-231 细胞的细胞侵袭。PTPα 不是类似于入侵伪足的 TKS5 阳性结构的组成部分；相反，PTPα 定位于对 MMP14、caveolin-1 和早期内体抗原 1 呈阳性的内体结构。此外，PTPα 调节 MMP14 对质膜突起的定位，表明 PTPα 在 MMP14 的细胞内运输中起作用。重要的是，我们发现缺乏 PTPα 的原位 MDA-MB-231 肿瘤对周围乳腺脂肪垫的侵袭减少。这些发现表明 PTPα 在调节三阴性乳腺癌细胞侵袭中的新作用。