Epithelial-mesenchymal transition (EMT) is a biological process during which epithelial cells lose their characteristic cell-cell adhesion and polarity, and acquire a mesenchymal phenotype with increased motility and invasiveness. This transition is essential for various physiological and pathological processes, such as embryonic development, tissue repair, and cancer progression.
During embryonic development, EMT plays a critical role in gastrulation, which is the process of forming the three germ layers (ectoderm, mesoderm, and endoderm) from the initial single-layered structure called the epiblast. EMT allows epithelial cells to undergo a transition into mesenchymal cells, which can then migrate and differentiate into various tissues and structures within the developing organism.
In tissue repair and wound healing, EMT is involved in the process of tissue regeneration and re-epithelialization. Epithelial cells at the edge of the wound undergo EMT to become more motile and invasive, allowing them to migrate and close the wound. Once the wound is closed, the cells can revert to their epithelial phenotype through a process called mesenchymal-epithelial transition (MET).
EMT is also implicated in cancer progression, particularly in the process of metastasis. Cancer cells that undergo EMT acquire invasive and migratory properties, enabling them to break away from the primary tumor, invade the surrounding tissues, and enter the bloodstream or lymphatic system. These circulating tumor cells can then travel to distant sites and form secondary tumors, a process known as metastasis. EMT is also associated with cancer cell resistance to various therapies, making it a significant area of study in cancer research.
Several signaling pathways and transcription factors, such as transforming growth factor-beta (TGF-β), Wnt, Notch, Snail, Slug, and Twist, are involved in the regulation of EMT. The transition is characterized by the downregulation of epithelial markers, such as E-cadherin, and the upregulation of mesenchymal markers, such as N-cadherin and vimentin. Understanding the molecular mechanisms underlying EMT may provide valuable insights into the development of new therapeutic strategies for cancer and other diseases.