Mutant B-Raf(V600E) promotes melanoma paracellular transmigration by inducing thrombin-mediated endothelial junction breakdown

Pu Zhang, Shan Feng, Gentao Liu, Heyong Wang, Huifeng Zhu, Qiao Ren, Huiyuan Bai, Changliang Fu, Cheng Dong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: A prothrombotic state is one of the hallmarks of advanced cancer. Results: B-Raf(V600E)-dependent thrombin release from metastatic melanoma signals focal adherens junction disassembly by triggering VE-cadherin phosphorylation and ubiquitination. Conclusion: Thrombin-mediated junction breakdown allows melanoma extravasation via a paracellular route. Significance: Targeting B-Raf(V600E)-mediated thrombin generation and endothelial barrier dysfunction may represent a novel therapeutic strategy to limit tumor metastasis.

Original languageEnglish (US)
Pages (from-to)2087-2106
Number of pages20
JournalJournal of Biological Chemistry
Volume291
Issue number5
DOIs
StatePublished - Jan 29 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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