Role of epithelial–mesenchymal transition in invasion and metastasis of breast cancers


Introduction Invasion and metastasis are the main causes for the death of patients with breast cancers. Epithelial–mesenchymal transition is implicated as a vital process in the invasion and metastasis of breast cancers, with endowing migratory and invasive cancer cells associated with metastatic capability. Increasing evidences demonstrated that epithelial–mesenchymal transition-initiating cells possessed mesenchymal features and stem-like traits that are resistant to chemotherapy. In this review, we summarise the physiological and pathological roles of epithelial–mesenchymal transitions, new insights in the molecular mechanisms of regulating epithelial–mesenchymal transition during breast cancer invasion and metastasis, and its implication in chemotherapy resistance. Conclusion Therefore, it is challenging to probe and uncover the mechanistic regulation of oncogenic epithelial–mesenchymal transition, which will contribute to our understanding of metastatic dissemination and the role of targeting epithelial– mesenchymal transition with existing therapy as well as developing new drugs, in order to prevent metastasis and to diminish distant recurrence in patients with breast cancers. Introduction Breast cancer is the most common malignant tumour, and only second to lung and bronchus cancer as the cause of cancer-related deaths in women, which is often due to the development of metastatic disease1. For improving targeted treatments and accurate prognoses of patients with breast cancers, a comprehensive understanding of the mechanism of metastasis is an urgent requirement. Epithelial–mesenchymal transition (EMT), which is known as the probable first step in the complex process of metastasis, is a distinctive morphological change, in which the series of events converting the epithelial cancer cells switch from a well-differentiated, adherent phenotype to an individual, invasive migratory mesenchymal cell2. EMT is vital for morphogenesis, such as physiological embryogenesis and histogenesis, and involved in multiple pathological processes, such as wound healing, renal fibrosis and tumour metastasis. EMT is mainly characterised by loss of E-cadherin (CDH1) expression and other special molecular changes that promote architectural changes, followed by the loss of cell–cell junction, cell–matrix adhesion and modulation of polarity, resulting in acquisition of mesenchymal features, such as spindle shape and increased migratory and invasive capacity2,3. On the other hand, EMT is also supposed to be associated with cancer stem cells (CSCs), by generating self-renewing cells, which is contributed to the tumorigenesis and multi-drug resistance4. The aim of this review was to discuss the role of EMT in invasion and metastasis of breast cancers. Discussion Epithelial–mesenchymal transition and its classification EMTs are involved in transdifferentiation of epithelial cells into mesenchymal cells under special physiological or pathological conditions. However, this process is reversible that the transdifferentiated migratory mesenchymal cells can re-generate epithelial cells, known as mesenchymal–epithelial transition (MET), or other cell types4. Based on different functional consequences, it is suggested to classify EMT into three biological subtypes3. Type 1 EMTs, associated with implantation of a fertilised egg, embryogenesis and organ formation, can generate diverse cell types with mesenchymal phenotypes and potential to subsequently undergo a MET2. Successive EMT and MET events model and define the architecture of different organs and tissues. Type 2 EMTs are involved in wound healing, organ fibrosis, such as kidney, liver and lung with epithelial cells. Under chronic inflammatory injury, the epithelial cells will express both biomarkers of epithelial phenotype, such as E-cadherin, and mesenchymal phenotype, such as fibroblast-specific protein 1, and finally undergo EMT to generate fibroblasts and other related cells for repair and reconstruction of tissues. Unlike type 1, type 2 EMTs, engage in response to inflammation or trauma, cease as the stimuli are ending and ongoing type 2 EMTs lead to organ destruction due to persistent inflammation5. * Corresponding author Email: † Both these authors contributed equally to this study. 1 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong Province, P.R. China 2 Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, P.R. China 3 Department of Oral Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

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@inproceedings{Liu2014RoleOE, title={Role of epithelial–mesenchymal transition in invasion and metastasis of breast cancers}, author={J Liu and J. S. Shen and J Hu and X Dou and G F Zhang}, year={2014} }