TY - JOUR
T1 - Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
AU - Yang, Jing
AU - Mani, Sendurai A.
AU - Donaher, Joana Liu
AU - Ramaswamy, Sridhar
AU - Itzykson, Raphael A.
AU - Come, Christophe
AU - Savagner, Pierre
AU - Gitelman, Inna
AU - Richardson, Andrea
AU - Weinberg, Robert A.
N1 - Funding Information:
We thank F. Miller, F. Perrin-Schmitt, R. Iggo, E. Fearon, and G. Christofori for reagents; I. Ben-Porath, S. Stewart, U. Muller, K. Hartwell, and other members of R.A.W.'s laboratory for critical review of the manuscript; F. Reinhardt, M. Brooks, and C. Ladd for technical help; J. Staunton and Z. Wang for advice on statistical analysis. We acknowledge the support of Whitehead Institute Functional Genomic Program (consortium partners including Affymetrix, Millennium, and Bristol-Mayers Squibb) and W.M. Keck Biological Imaging Facility at Whitehead Institute. J.Y. is a recipient of postdoctoral fellowships from Damon Runyon Cancer Research Foundation, NIH NRSA award (1 F32 CA101507) and the Margaret and Herman Sokol Fellowship in Biomedical Research. S.A.M. is a recipient of postdoctoral fellowship from US Army Breast Cancer Research Program (DAMD17-01-1-0457). R.A.W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Cancer Research Professor. This research is supported by NIH grant R21-CA096689 (R.A.W.), P01-CA80111 (R.A.W.), MIT/Ludwig Fund for Cancer Research (R.A.W.), and Harvard SPORE in Breast Cancer (A.R.).
PY - 2004/6/25
Y1 - 2004/6/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=2942707848&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2004.06.006
DO - 10.1016/j.cell.2004.06.006
M3 - Article
AN - SCOPUS:2942707848
SN - 0092-8674
VL - 117
SP - 927
EP - 939
JO - Cell
JF - Cell
IS - 7
ER -
