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

Natalia I Díaz-Valdivia1, Jorge Díaz1,2, Pamela Contreras1

  • 1Cellular Communication Laboratory, Center for studies on Exercise, Metabolism and Cancer (CEMC), Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago, Chile.

Oncogene
|March 11, 2020
PubMed

Insights

The protein tyrosine phosphatase PTPN14 dephosphorylates caveolin-1 (CAV1), inhibiting cancer cell migration and metastasis. Overexpressing PTPN14 reduces CAV1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Caveolin-1 (CAV1) promotes cancer cell migration, invasion, and metastasis.
  • E-cadherin co-expression inhibits CAV1's metastasis-promoting functions, but the mechanism is unclear.
  • The interaction between CAV1, E-cadherin, and β-catenin in metastasis regulation requires further elucidation.

Purpose of the Study:

  • To identify proteins interacting with CAV1 in the presence of E-cadherin.
  • To investigate the role of protein tyrosine phosphatase PTPN14 in CAV1-mediated metastasis.
  • To determine if PTPN14 can regulate CAV1 activity and cancer cell behavior.

Main Methods:

  • Mass spectrometry to analyze protein complexes involving CAV1.
  • Co-immunoprecipitation and Western blotting to confirm protein interactions.
  • Functional assays measuring cell migration, invasion, and Rac-1 activation.
  • In vivo metastasis assays in a murine melanoma model.

Main Results:

  • The protein tyrosine phosphatase PTPN14 was identified in CAV1 immunoprecipitates when E-cadherin was co-expressed.
  • PTPN14 directly interacts with CAV1, and this interaction is independent of E-cadherin for the CAV1(Y14F) mutant.
  • Overexpression of PTPN14 reduced CAV1 phosphorylation, suppressed CAV1-enhanced cell migration, invasion, and Rac-1 activation, and inhibited metastasis in vivo.

Conclusions:

  • CAV1 is a novel substrate for the protein tyrosine phosphatase PTPN14.
  • PTPN14 negatively regulates CAV1 activity and suppresses its pro-metastatic functions.
  • PTPN14 overexpression is sufficient to reduce CAV1-induced metastasis, highlighting its therapeutic potential.

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