@article{9b862c0ebf82480392aa4e2e4c4dfdb3,
title = "RAC1 activation mediates Twist1-induced cancer cell migration",
abstract = "Epithelial-mesenchymal transition (EMT), which is characterized by the suppression of the adhesion protein E-cadherin, is a crucial process that promotes metastasis and stem-like properties of cancer cells. However, the dissociation of cellular aggregates is not sufficient to explain why cancer cells move, and the motile nature of cancer cells undergoing EMT remains elusive. Here, we identify a mechanism in which the EMT inducer Twist1 elicits cancer cell movement through activation of RAC1. Twist1 cooperates with BMI1 to suppress let-7i expression, which results in upregulation of NEDD9 and DOCK3, leading to RAC1 activation and enabling mesenchymal-mode movement in three-dimensional environments. Moreover, the suppression of let-7i contributes to Twist1-induced stem-like properties. Clinically, activation of the Twist1-let-7i-NEDD9 axis in head and neck cancer patients correlates with tumour invasiveness and worse outcome. Our results uncover an essential mechanism to explain how Twist1 induces the motile stem-like cancer cell phenotype beyond simply suppressing E-cadherin.",
author = "Yang, {Wen Hao} and Lan, {Hsin Yi} and Huang, {Chi Hung} and Tai, {Shyh Kuan} and Tzeng, {Cheng Hwai} and Kao, {Shou Yen} and Wu, {Kou Juey} and Hung, {Mien Chie} and Yang, {Muh Hwa}",
note = "Funding Information: We thank M. F. Olson (The Beaston Institute for Cancer Research, UK) for providing the ROCK–ER-WT and ROCK–ER-K121G plasmids, and H. Kimura (National Institute of Neuroscience, Tokyo, Japan) for the pCl–neo–DOCK3HA plasmid. We thank T. Z. Huang, Y. B. Khotskaya, C. W. Lee and S. S. Chang (M. D. Anderson Cancer Center, Texas, USA) for critical comments on the manuscript. We thank C. H. Lin and H. W. Liu (National Yang-Ming University, Taiwan) for supporting the time-lapse microscopy techniques. This work was supported by the National Health Research Institutes (NHRI-EX100-10037BI to M-H.Y.; NHRI-EX100-9931BI to K-J.W.); the National Science Council (NSC 99-2314-B-010-007-MY3 and 100-2321-B-010-015 to M-H.Y.; NSC 100-2321-B-039-002 to M-C.H.); Taipei Veterans General Hospital (VGH 100-C-088, 101-C-005 to M-H.Y.); Veterans General Hospitals University System of Taiwan Joint Research Program (VGHUST101-G7-4-1 to M-H.Y.); a grant from the Ministry of Education, Aim for the Top University Plan (to M-H.Y.); a grant from the Department of Health, Center of Excellence for Cancer Research (DOH100-TD-C-111-007 to M-H.Y; DOH101-TD-C-111-005 to M-C.H.); and the Sister Institution Fund of China Medical University and Hospital and MD Anderson Cancer Center.",
year = "2012",
month = apr,
doi = "10.1038/ncb2455",
language = "English",
volume = "14",
pages = "366--374",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "4",
}
