The epithelial-mesenchymal transition (EMT) and colorectal cancer progression.
During embryonic development, epithelial cells must escape the structural constraints imposed by tissue architecture and adopt a phenotype more amenable to cell movement, a process known as the epithelial-mesenchymal transition (EMT). The progression of carcinomas to invasive and metastatic disease may also involve localized occurrences of EMT. However, data that support the actual occurrence of EMT in specific carcinomas and the relevance of this process to the progression of these tumors had been scant. This review highlights recent studies that substantiate the importance of the EMT to colorectal carcinoma. Specifically, a novel model for studying the EMT of colorectal carcinoma has been used to gain insight into the nature of the EMT itself and to identify molecular events that contribute to disease progression. Although loss of E-cadherin function is a primal event for the EMT, the expression of specific integrins such as alpha(v)beta6 as a consequence of the EMT enables invasive cells to interact with interstitial matrices and to sustain activation of TGF-beta. Of note, alpha(v)beta6 expression in tumors is a marker of cells that have undergone an EMT and it is prognostic for tumors that will progress more rapidly to terminal disease. The EMT also induces autocrine signaling involving VEGF and Flt-1 that enable invasive cells to become 'self-sufficient' for survival. Thus, the EMT appears to be an integral component of colorectal cancer progression and its analysis can yield novel targets for prognosis and therapy.
Bates
Richard C
RC
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachussetts, USA. richard.bates@umassmed.edu
Mercurio
Arthur M
AM
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016023:Integrins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C073878:integrin alphavbeta6