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Twist2 contributes to breast cancer progression by promoting an epithelial–mesenchymal transition and cancer stem-like cell self-renewal

Oncogene volume 30, pages 4707–4720 (2011)Cite this article

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Abstract

The epithelial to mesenchymal transition (EMT) is a highly conserved cellular programme that has an important role in normal embryogenesis and in cancer invasion and metastasis. We report here that Twist2, a tissue-specific basic helix-loop-helix transcription factor, is overexpressed in human breast cancers and lymph node metastases. In mammary epithelial cells and breast cancer cells, ectopic overexpression of Twist2 results in morphological transformation, downregulation of epithelial markers and upregulation of mesenchymal markers. Moreover, Twist2 enhances the cell migration and colony-forming abilities of mammary epithelial cells and breast cancer cells in vitro and promotes tumour growth in vivo. Ectopic expression of Twist2 in mammary epithelial cells and breast cancer cells increases the size and number of their CD44high/CD24low stem-like cell sub-populations, promotes the expression of stem cell markers and enhances the self-renewal capabilities of stem-like cells. In addition, exogenous expression of Twist2 leads to constitutive activation of STAT3 (signal transducer and activator of transcription 3) and downregulation of E-cadherin. Thus, the overexpression of Twist2 may contribute to breast cancer progression by activating the EMT programme and enhancing the self-renewal of cancer stem-like cells.

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Acknowledgements

We thank Professor Kunxin Luo (Department of Molecular and Cell Biology, University of California, Berkeley), Professor Shideng Bao (Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic) and reviewers for critical comments. This work was supported by grants from the National Nature Science Foundation of China (no. 30871242, 31071302), National Basic Research Program of China (no. 2009CB941601, 2010CB732402), the Fundamental Research Funds for the Central Universities (no. 2010121095), the Science Planning Program of Fujian Province (2009J1010), the Outstanding Young Science Foundation of Fujian Province (no. 2010J06013) and the 985 Project grant from Xiamen University.

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  1. X Fang and Y Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China

    X Fang, Y Cai, J Liu, Z Wang, L Yuan & G Ouyang

  2. Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China

    Q Wu & Z Zhang

  3. College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China

    C J Yang

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  1. X Fang
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Correspondence to G Ouyang.

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Fang, X., Cai, Y., Liu, J. et al. Twist2 contributes to breast cancer progression by promoting an epithelial–mesenchymal transition and cancer stem-like cell self-renewal. Oncogene 30, 4707–4720 (2011). https://doi.org/10.1038/onc.2011.181

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