Cdc42 promotes transendothelial migration of cancer cells through β1 integrin

Nicolas Reymond, Jae Hong Im, Ritu Garg, Francisco M Vega, Barbara Borda d'Agua, Philippe Riou, Susan Cox, Ferran Valderrama, Ruth J Muschel, Anne J Ridley

Research output: Contribution to journalArticle (Academic Journal)peer-review

122 Citations (Scopus)


Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell-endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.

Original languageEnglish
Pages (from-to)653-68
Number of pages16
JournalJournal of Cell Biology
Issue number4
Publication statusPublished - 12 Nov 2012


  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cells, Cultured
  • Endothelial Cells
  • Fibronectins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin beta1
  • Lung Neoplasms
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Protein Transport
  • Serum Response Factor
  • Transcription, Genetic
  • Transendothelial and Transepithelial Migration
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein
  • Journal Article
  • Research Support, Non-U.S. Gov't


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