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The Protein Tyrosine Phosphatase DEP-1/PTPRJ Promotes Breast Cancer Cell Invasion and Metastasis

The Protein Tyrosine Phosphatase DEP-1/PTPRJ Promotes Breast Cancer Cell Invasion and Metastasis

K Spring, P Fournier, L Lapointe, C Chabot, J Roussy, S Pommey, J Stagg, I Royal

Oncogene. 2015 Oct 29;34(44):5536-47.

PMID: 25772245

Abstract:

DEP-1/PTPRJ is a receptor-like protein tyrosine phosphatase mainly known for its antiproliferative and tumor-suppressive functions. Many identified substrates are growth factor receptors, and DEP-1 is deleted and/or mutated in human cancers including that of the breast. However, DEP-1 was also identified as a promoter of Src activation and proinvasive functions in the endothelium, suggesting it could perhaps mediate breast cancer invasiveness that is likewise driven by Src family kinases. We show here that DEP-1 expression was greater in highly invasive breast cancer cells (MDA-MB-231, Hs578T, BT-549) than in the less invasive or untransformed cell lines tested (MCF-7, T47D, SK-BR3 and MCF10A). DEP-1 silencing experiments in invasive cells demonstrated that moderately expressed and catalytically active DEP-1 was required, in collaboration with basal epidermal growth factor receptor activity, for Src activation and the phosphorylation of its substrate Cortactin, and for their colocalization at the cell's leading edge. This correlated with an increased number of cell protrusions, and an enhanced capacity of the cells to migrate and invade. Similarly, moderate overexpression of DEP-1 in the low-invasive cells resulted in the promotion of their invasiveness in an Src-dependent manner. Consistent with these data, the expression of endogenous DEP-1 was elevated in a bone metastatic cell line derived from MDA-MB-231 cells, and promoted increased Src Y418 and Cortactin Y421 phosphorylation, as well as pro-MMP9 secretion and Matrigel invasion. Importantly, the silencing of DEP-1 in MDA-MB-231 cells greatly decreased their ability to metastasize, despite having no effect on tumor growth or angiogenesis. Hence, we found that moderate expression of DEP-1 was associated with the increased relapse and decreased survival of breast cancer patients. These results therefore identify a new and unsuspected role for DEP-1 as a mediator of an invasive cell program implicating Src activation and the promotion of breast cancer progression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417918	DEP1 Active human			Price

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