Epithelial mesenchymal transition in colorectal cancer: Seminal role in promoting disease progression and resistance to neoadjuvant therapy

Background: Epithelial mesenchymal transition (EMT) may be physiological as part of embryological development, or pathological as part of cancer development. It is one of the key initiating events in the metastatic cascade. EMT has profound effects on tumour cell invasiveness, proliferation and motility. In the present article we aimed to review the potential role of EMT as a process to explain colorectal cancer progression and resistance to neoadjuvant therapy. Methods: Extensive literature searches were performed in Pubmed, EMBASE and Google Scholar databases to identify relevant articles published before March 2012. Results: There is adequate evidence to support the complex upstream signalling alterations needed for EMT to occur in colorectal cancers. Changes of EMT are likely to be found at the tumour invasive front: the deepest, growing tumour margin. Loss of E-cadherin at the cell membrane causes loss of cellular integrity, with subsequent migration of malignant cells and tumour budding. These processes are associated with metastases and recurrence of colorectal cancer. There is early evidence from a limited number of studies that resistance to neoadjuvant therapy in colorectal cancer is associated with changes of EMT. However, there is a lack of supporting evidence originating from human colorectal cancer tissues. Conclusions: Emerging evidence demonstrates that development of EMT in colorectal cancer leads to an aggressive phenotype that may promote metastatic spread, and augment treatment resistance during neoadjuvant therapy. A clearer understanding of the processes and role of EMT in colorectal cancer may also highlight novel therapeutic strategies. (C) 2012 Elsevier Ltd. All rights reserved.