The non-receptor tyrosine phosphatase type 14 blocks caveolin-1-enhanced cancer cell metastasis.

Abstract

Caveolin-1 (CAV1) enhanced migration, invasion, and metastasis of cancer cells is inhibited by co-expression of the glycoprotein E-cadherin. Although the two proteins form a multiprotein complex that includes β-catenin, it remained unclear how this would contribute to blocking the metastasis promoting function of CAV1. Here, we characterized by mass spectrometry the protein composition of CAV1 immunoprecipitates from B16F10 murine melanoma cells expressing or not E-cadherin. The novel protein tyrosine phosphatase PTPN14 was identified by mass spectrometry analysis exclusively in co-immunoprecipitates of CAV1 with E-cadherin. Interestingly, PTPN14 is implicated in controlling metastasis, but only few known PTPN14 substrates exist. We corroborated by western blotting experiments that PTPN14 and CAV1 co-inmunoprecipitated in the presence of E-cadherin in B16F10 melanoma and other cancer cells. Moreover, the CAV1(Y14F) mutant protein was shown to co-immunoprecipitate with PTPN14 even in the absence of E-cadherin, and overexpression of PTPN14 reduced CAV1 phosphorylation on tyrosine-14, as well as suppressed CAV1-enhanced cell migration, invasion and Rac-1 activation in B16F10, metastatic colon [HT29(US)] and breast cancer (MDA-MB-231) cell lines. Finally, PTPN14 overexpression in B16F10 cells reduced the ability of CAV1 to induce metastasis in vivo. In summary, we identify here CAV1 as a novel substrate for PTPN14 and show that overexpression of this phosphatase suffices to reduce CAV1-induced metastasis.

• Authors: Natalia I Díaz-Valdivia, Jorge Díaz, Pamela Contreras, América Campos, Victoria Rojas-Celis, Renato A Burgos-Ravanal, Lorena Lobos-González, Vicente A Torres, Viviana I Perez, Balz Frei, Lisette Leyton, Andrew F G Quest
• Journal: Oncogene (Oncogene) Vol. 39 Issue 18 Pg. 3693-3709 (04 2020) ISSN: 1476-5594 [Electronic] England
• PMID: 32152405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, mouse
• Cadherins
• Cav1 protein, mouse
• Caveolin 1
• beta Catenin
• PTPN14 protein, mouse
• Protein Tyrosine Phosphatases, Non-Receptor

Topics

• Animals
• Cadherins (genetics)
• Caveolin 1 (genetics)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Melanoma, Experimental (genetics, pathology)
• Mice
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Phosphorylation (genetics)
• Protein Tyrosine Phosphatases, Non-Receptor (genetics)
• beta Catenin (genetics)