Mesenchymal transition is a biological process during which cells undergo a shift in their phenotype from a more organized, adherent state to a more motile and invasive state. The most well-known and studied type of mesenchymal transition is the epithelial-mesenchymal transition (EMT).
During EMT, epithelial cells lose their cell-cell adhesion and apical-basal polarity, which are characteristic features of epithelial tissues. This results in the downregulation of epithelial markers, such as E-cadherin, and the upregulation of mesenchymal markers, such as N-cadherin and vimentin. The cells acquire a mesenchymal phenotype, enabling them to migrate and invade surrounding tissues.
MT plays a crucial role in various physiological and pathological processes, including:
- Embryonic development: It is essential for gastrulation, a critical stage of embryonic development during which the three germ layers (ectoderm, mesoderm, and endoderm) are formed. The process allows cells to migrate and differentiate into various tissues and structures within the developing organism.
- Tissue repair and wound healing: It is involved in tissue regeneration and re-epithelialization during the healing process. Epithelial cells at the edge of a wound undergo mesenchymal transition 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).
- Cancer progression: It has been implicated in cancer progression, particularly in the process of metastasis. Cancer cells that undergo mesenchymal transition 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. Mesenchymal transition is also associated with cancer cell resistance to various therapies, making it a significant area of study in cancer research.
Various 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 mesenchymal transition. Understanding the molecular mechanisms underlying mesenchymal transition may provide valuable insights into the development of new therapeutic strategies for cancer and other diseases.