The epithelial to mesenchymal transition (EMT) describes the processes that convert epithelial cells into mesenchymal cells. This happens through the loss of polarity and cell-cell adhesions in the epithelial cells, along with the onset of capabilities to migrate, proliferate, differentiate, and develop into specific tissues and organs.
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Significance of the epithelial-mesenchymal transition
While their function and activity is not yet fully understood, research has shown that mesenchymal cells are key to tissue repair and pathological processes. They are also implicated in tissue fibrosis, tumor invasiveness, and metastasis.
There is a growing body of evidence that hints at epithelial-mesenchymal transitions being activated during the disease process. It has been seen that chronically inflamed tissues and neoplasia appropriate epithelial-mesenchymal transitions, and researchers are now aiming to identify the pathways that lead to its activation in order to develop new therapeutic interventions.
How do epithelial-mesenchymal transitions occur?
Epithelial cells, which are an essential unit of many of the body's organs, are usually polarized and interact with the basement membrane through its basal surface.
During the biological process of epithelial-mesenchymal transition, the epithelial cell goes through a series of changes that convert it into a mesenchymal cell, giving it properties such as an improved migratory capacity, invasiveness, increased resistance to apoptosis, and a vastly improved production of extracellular matrix components.
The characteristic arrangement of epithelial cells into cohesive sheets, securely attaching them to one another, is eradicating during epithelial-mesenchymal transitions. This part of the process signifies the completion of the transition, at which point the newly formed mesenchymal cells become free from the epithelial layer.
The initiation of the transition is instituted by molecular processes such as activation of transcription factors, production of ECM-degrading enzymes, expression of certain cell-surface proteins, reorganization, and expression of cytoskeletal proteins, and changes in the expression of specific microRNAs.
The processes that occur as part of the transition are reversible, and for this reason, the name was changed from "epithelial-mesenchymal transformation" to "epithelial-mesenchymal transition" to reflect the fact that the outcomes of the process are changeable.
Mesenchymal-epithelial transition (MET) represents the reverse transition, in which mesenchymal cells are converted into epithelial cells. Unfortunately, this process is poorly understood, and much more work needs to be done to gain a firm grasp of how it works.
Implications for cancer treatment
The process of epithelial to mesenchymal transition has been implicated in the establishment and growth of cancerous cells. A growing body of research is uncovering the key role that this transition plays in tumor progression, metastasis, and resistance to treatment. Studies are continuing to look into the significance of epithelial to mesenchymal transition in the journey of different kinds of cancer, and are looking to it to provide new ways to deliver effective treatments.
In 2008 scientists came together and classified the three subtypes of epithelial to mesenchymal transition. The first of these is related to the function of generating mesenchymal cells, along with the reverse process. The second type is characterized by its function in healing wounds, regenerating tissue regeneration, and fibrosis.
The last, type three, was classified as transitions that take place in epithelial neoplastic cells when going through genetic and epigenetic changes. It's this third type that scientists have discovered is related to cancer progression. In epithelial cancers, such as pancreatic cancer, type three epithelial to mesenchymal transitions have been identified as being involved in the invasion, dissemination, and metastasis stages.
During the transition process, it has been seen that cells can acquire molecular alterations that may support the development of dysfunctional junctions and adhesions between cells, and impact their morphology. Cancer cell invasion and progression is supported by both of these factors.
A wide body of evidence has built up that has drawn attention to the significance of confirming complex molecular signaling pathways that control epithelial to mesenchymal transition and cancer stem cells in pancreatic cancer.
This identification is important at the stages of monitoring tumor formation, progression, and response to therapy. Scientists are working on ways that they can improve clinical outcomes by taking advantage of what has been learned of the role of epithelial to mesenchymal transition in cancer.
Currently, while the transition process has been implicated in the establishment and maintenance of cancer, scientists admit there is not enough data to fully explain the key underlying molecular networks involved that would give a full understanding of how it contributes to malignant tumor progression.
Attaining an understanding of the behavior of these specific molecular pathways could potentially lead to the development of more effective treatment strategies. Studies into patients with breast cancer found that tumor-initiating cells that have the capacity to regenerate all cell types in a tumor are elevated in breast cancer patients following treatment.
Further to this, they found that in the "claudin-low" subtype of breast cancer, tumor-initiating cells are characterized by a high expression of markers related to epithelial-mesenchymal transition. Researchers theorized that there is a direct link between the gain of tumor-initiating cell properties and epithelial to mesenchymal transitions.
Through further study, it is believed that new therapies may be able to be developed that target the specific molecular pathways related to epithelial to mesenchymal transitions, which could be delivered together with other traditional therapies to improve the treatment effectiveness.
Sources:
- Creighton, C., Chang, J. and Rosen, J. (2010). Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer. Journal of Mammary Gland Biology and Neoplasia, 15(2), pp.253-260. https://doi.org/10.1007/s10911-010-9173-1
- Diepenbruck, M. and Christofori, G. (2016). Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe?. Current Opinion in Cell Biology, 43, pp.7-13. https://doi.org/10.1016/j.ceb.2016.06.002
- Kalluri, R. and Weinberg, R. (2009). The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 119(6), pp.1420-1428. https://doi.org/10.1172/JCI39104
- Savagner, P. (2010). The epithelial-mesenchymal transition (EMT) phenomenon. Annals of Oncology, 21(Supplement 7), pp.vii89-vii92. https://doi.org/10.1172/JCI39104
- (2014). Epithelial Cells - an overview. Handbook of Nanosafety. https://www.sciencedirect.com/topics/neuroscience/epithelial-cells.
- Zhou, P., Li, B., Liu, F., Zhang, M., Wang, Q., Liu, Y., Yao, Y. and Li, D. (2017). The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer. Molecular Cancer, 16(1). https://dx.doi.org/10.1186%2Fs12943-017-0624-9
Further Reading
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