Pegah Asadi,1,*
1. Department of Biological science and technologies , Hamedan Branch, Islamic Azad University, Hamedan, Iran
Introduction: The process of epithelial-to-mesenchymal transition involves the transformation of immobile epithelial cells into a mobile mesenchymal phenotype and was first observed during early development. EMT is involved in embryonic processes such as gastrulation, neural crest formation, and heart development. It also plays a critical role in physiological processes such as healing wounds and maintaining tissue balance. It is important to note that the abnormal reactivation of the EMT process is a key factor in diseases such as organ fibrosis or the progression of cancer to metastasis, which is the main focus of this article.
Methods: Cancer cells can utilize classical EMT functions to move, infiltrate, and enter both blood and lymphatic vessels. Additionally, nonclassical EMT characteristics aid in the onset of tumors and the spread of metastases.
Classical:
Migration and invasion:In regular epithelial tissue, cells create continuous protective layers that are essential for maintaining their structural integrity.
Various junction complexes like adherens, desmosomes, and tight junctions connect epithelial cells, supporting their polarity and preventing the passage of solutes and water. These cell connections are critical for tissue function and are disturbed during the epithelial-mesenchymal transition (EMT). EMT results in the loss of polarity, changes in the cytoskeleton, and heightened motility in tumor cells. Additionally, EMT facilitates invasion by breaking down basement membranes and the extracellular matrix.
Non-classical EMT features:
Regulation of stemness:Tumor heterogeneity remains unchanged following the transplantation of single tumor cells into mice, prompting research into the stemness of cancer cells. Instances of this phenomenon can be observed in breast cancer, pancreatic cancer, and squamous cell carcinoma, where critical elements such as SNAI1, TWIST1, and ZEB1 control the characteristics of stem cells. The process of epithelial-mesenchymal transition (EMT) plays a vital role in the onset of tumors, metastasis, and invasion. EMT-inducing transcription factors (EMT-TFs) like PRRX1 and ZEB2 have an impact on the progression of cancer. It is crucial to comprehend the adaptability of EMT and the characteristics of stemness in order to effectively address the growth and spread of tumors.
Therapy resistance:Standard treatment focuses on cells that are not similar to stem cells and encounters difficulties with those that have stem cell characteristics activated by EMT. The gene patterns of EMT are connected to resistance to treatment. Different mechanisms, such as the removal of drugs and avoidance of cell death, contribute to the development of resistance. Lowering ZEB1 expression increases the responsiveness to treatment in specific cancer cells. EMT is linked to heightened resistance to chemotherapy in various types of cancer. EMT transcription factors play a critical role in coordinating these processes.
Metabolic reprogramming:Metabolic rewiring is significant for cancer cells to support their quick development in spite of restricted oxygen supply. Glucose, lipid, and amino corrosive digestion system changes back metastasis by enacting EMT program. Cancer cells display modified glycolysis and triglyceride pathways, advancing the "Warburg impact" indeed in oxygen-rich situations. Upregulation of glucose transporters like GLUT1 and GLUT3 advance improves glycolysis. Lacks within the TCA cycle can moreover encourage EMT. EMT-associated quality expression modifications uncover a mesenchymal metabolic signature controlled by TWIST1. Changes in greasy corrosive digestion system, layer ease, and lipid composition moreover contribute to EMT movement and metastasis.
EMT and immune evasion:In the course of tumor development, cancer cells devise methods to avoid immune reactions triggered by new tumor antigens, including concealing antigens and establishing an immune-suppressing surroundings. This is frequently linked to EMT, during which EMT-TFs oversee these activities. EMT-related processes can disrupt antigen demonstration and facilitate the attraction of Tregs, impeding CTL function. EMT cells might escape immune responses by reducing antigen presentation or triggering immune checkpoints.
Results: Therapeutic options to target EMT:The presence of epithelial-to-mesenchymal transition (EMT) in cancer is associated with unfavorable treatment outcomes. Treatment approaches such as standard care, targeted therapy, and surgery may induce EMT, resulting in treatment resistance. Inhibiting EMT-associated pathways using compounds like miRNAs or HDAC inhibitors can potentially reverse this process and improve treatment response. Nevertheless, it is important to weigh the possible downsides, considering that EMT plays crucial roles in physiological activities such as wound healing and stem cell maintenance. It is vital to carefully assess the advantages of EMT inhibition against the potential drawbacks of interfering with normal tissue functions. A thorough understanding of the complexities of EMT in cancer is crucial to develop effective treatment plans.
Conclusion: In summary Embryonic morphogenesis relies on the essential process of epithelial mesenchymal transition. During this process, cells lose their epithelial characteristics and integrity, gain mesenchymal features, and develop the ability to move. The cancer exploits this process to induce crucial alterations in shape and movement, which drive its spread. Furthermore, EMT is more and more recognized as the coordinator of a wide range of additional characteristics of cancer, including the ability of tumor cells to function as stem cells, their capacity to form tumors, their resistance to treatment, and their ability to adjust to changes in the surrounding environment.