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 coimmunoprecipitates 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 coinmunoprecipitated 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.

The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers

“…And mutated PTPN14 is suggested to be a tumor suppressor gene for colorectal cancer, regulating cellular pathways that are appropriate for therapeutic intervention [28]. A recent study proved that PTPN14 suffices to inhibit migration and invasion of metastatic cancer cells [44]. In a xenograft breast cancer model, PTPN14 acts as a suppressor of metastasis of triple-negative breast cancer cells [45].…”

Protein tyrosine phosphatases in cell adhesion

“…PTPRK was recently highlighted as a regulator of the EMT hybrid state [ 215 ], consistent with previous findings where PTPRK KO cells exhibited reduced junctional integrity and cell height, but did not undergo a full transition to a mesenchymal state [ 22 ]. PTPN9 overexpression suppressed invasion in breast cancer [ 216 ] and PTPN14 overexpression correlates with decreased invasion in several cancer cell lines [ 217 ]. In melanoma cells, PTPN14 interacts with and negatively regulates caveolin1 (CAV1) phosphorylation, preventing Rac1-mediated invasion [ 217 ].…”

“…PTPN9 overexpression suppressed invasion in breast cancer [ 216 ] and PTPN14 overexpression correlates with decreased invasion in several cancer cell lines [ 217 ]. In melanoma cells, PTPN14 interacts with and negatively regulates caveolin1 (CAV1) phosphorylation, preventing Rac1-mediated invasion [ 217 ]. PTPs can also promote invasion including PTPRU in glioma [ 218 ], PTPRJ in breast cancer [ 219 ], PTPRA in colon cancer [ 220 ] and PTPRZ in gastric cancer [ 221 ].…”

In Vitro Magnetic Techniques for Investigating Cancer Progression

“…A subset of common in vitro magnetic techniques involves the use of antibodyfunctionalized magnetic beads to sort a desired population out of a bulk culture. These include using magnetic associated cell sorting (MACS), isolating extracellular vesicles released by cancerous cells, and pulling down DNA, RNA, or specific proteins from lysed cells for quantification [105][106][107][108][109][110][111]. Magnetic particles have even been proposed as a method to improve transduction efficiency in conjunction with standard lentiviral particle use or instead of it [112][113][114].…”