Epithelial-mesenchymal transition and colorectal cancer: gaining insights into tumor progression using LIM 1863 cells

Abstract

In addition to allowing epithelial cells to escape the structural constraints imposed by tissue architecture and adopt a phenotype more amenable to cell movement, it is now recognized that the epithelial-mesenchymal transition (EMT) may also represent a critical component permitting the progression of carcinomas towards invasive and metastatic disease. However, data supporting the actual occurrence of EMT in specific solid tumors and its relevance to the process of progression of these cancers has been scant. Despite an extensive knowledge of the genetic basis for colorectal cancer, the translation of this information into effective treatments has been limited. Clearly, there is a desperate need for new and improved therapies and since the switch to a metastatic phenotype is critical for outcome, it is of paramount importance to elucidate the biology that underlies the progression of this disease. Thus, the unique LIM 1863 model for studying the EMT of colorectal carcinoma has been used to both substantiate the importance of the transition for this cancer type and to identify molecular events that contribute to disease progression. Importantly, it has emerged that not only does EMT enhance migratory capacity, but also elicits additional selective advantages to colonic tumor cells. Specifically, the acquisition of autocrine growth factor signaling loops, mechanisms to evade apoptosis, and expression of specific integrins allowing invasive cells to interact with interstitial matrices and sustain activation of TGF-beta combine to provide a compelling new biochemical framework for understanding how EMT contributes to tumor evolution.