Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis

Jing Yang, Sendurai A. Mani, Joana Liu Donaher, Sridhar Ramaswamy, Raphael A. Itzykson, Christophe Come, Pierre Savagner, Inna Gitelman, Andrea Richardson, Robert A. Weinberg

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis is a multistep process during which cancer cells disseminate from the site of primary tumors and establish secondary tumors in distant organs. In a search for key regulators of metastasis in a murine breast tumor model, we have found that the transcription factor Twist, a master regulator of embryonic morphogenesis, plays an essential role in metastasis. Suppression of Twist expression in highly metastatic mammary carcinoma cells specifically inhibits their ability to metastasize from the mammary gland to the lung. Ectopic expression of Twist results in loss of E-cadherin-mediated cell-cell adhesion, activation of mesenchymal markers, and induction of cell motility, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT). In human breast cancers, high level of Twist expression is correlated with invasive lobular carcinoma, a highly infiltrating tumor type associated with loss of E-cadherin expression. These results establish a mechanistic link between Twist, EMT, and tumor metastasis.

Original languageEnglish (US)
Pages (from-to)927-939
Number of pages13
JournalCell
Volume117
Issue number7
DOIs
StatePublished - Jun 25 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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