The well-defined series of genetic events accompanying the adenoma to carcinoma axis has been an essential paradigm in understanding the initiation and progression of colorectal cancer (CRC). Nonetheless, it is also clear that considerable heterogeneity exists in therapeutic response and disease progression, implying the presence of several different subtypes of cells, many of which clonally evolve in the course of the disease. One major factor in such a clonal evolution of CRC cells is the process of epithelial to mesenchymal plasticity that entails a broad continuum of genetic, epigenetic and metabolic alterations in cancer cells and can affect metastatic spread as well as enhance resistance to therapy. Better understanding of the determinants leading to epithelial to mesenchymal plasticity can help in prognostic stratification and identification of patients who will best respond to therapy.
A well-known paradigm for metastatic spread is the acquisition of mesenchymal characteristics by epithelial cells (epithelial to mesenchymal transition, EMT), which allows cells to intravasate into the circulation, extravasate to a target organ and upon re-acquisition of epithelial properties (mesenchymal to epithelial transition, MET) form macrometastases. Despite strong support for this paradigm, it is constantly challenged due to lack of unequivocal evidence and emergence of conflicting data on whether EMT is essential for metastasis. One hypothesis that has been proposed in recent years is the concept of partial/intermediate EMT, which entails the acquisition of mesenchymal properties while retaining epithelial characteristics, suggesting considerable plasticity in the disseminating tumor cells. Cells that acquire partial or hybrid EMT states enable migration in clusters and have robust stemness characteristics, as well resistance to drugs compared to cells that undergo complete EMT. Tumor budding, long known to predict poor prognosis in CRC, is likely to be made of clusters of cells that are undergoing partial EMT. The mechanistic underpinnings and signaling pathways for such a complex process need to be understood better for more effective therapeutic interventions.
The aim of the current Research Topic is to cover promising, recent, and novel research trends in the field of epithelial to mesenchymal plasticity in CRC. Areas to be covered in this Research Topic may include, but are not limited to:
· Transcriptional, post transcriptional and post translational regulation of expression of epithelial and mesenchymal markers.
· Mechanism and functional analysis of drug resistance and/or reversal of drug resistance in CRC cells undergoing partial EMT.
· Biomarkers that can predict the induction of partial EMT.
· Role of stressors such as nutrient restriction or hypoxia in the induction of partial EMT.
· Theoretical and computational models that help understand EM transition and plasticity.
The well-defined series of genetic events accompanying the adenoma to carcinoma axis has been an essential paradigm in understanding the initiation and progression of colorectal cancer (CRC). Nonetheless, it is also clear that considerable heterogeneity exists in therapeutic response and disease progression, implying the presence of several different subtypes of cells, many of which clonally evolve in the course of the disease. One major factor in such a clonal evolution of CRC cells is the process of epithelial to mesenchymal plasticity that entails a broad continuum of genetic, epigenetic and metabolic alterations in cancer cells and can affect metastatic spread as well as enhance resistance to therapy. Better understanding of the determinants leading to epithelial to mesenchymal plasticity can help in prognostic stratification and identification of patients who will best respond to therapy.
A well-known paradigm for metastatic spread is the acquisition of mesenchymal characteristics by epithelial cells (epithelial to mesenchymal transition, EMT), which allows cells to intravasate into the circulation, extravasate to a target organ and upon re-acquisition of epithelial properties (mesenchymal to epithelial transition, MET) form macrometastases. Despite strong support for this paradigm, it is constantly challenged due to lack of unequivocal evidence and emergence of conflicting data on whether EMT is essential for metastasis. One hypothesis that has been proposed in recent years is the concept of partial/intermediate EMT, which entails the acquisition of mesenchymal properties while retaining epithelial characteristics, suggesting considerable plasticity in the disseminating tumor cells. Cells that acquire partial or hybrid EMT states enable migration in clusters and have robust stemness characteristics, as well resistance to drugs compared to cells that undergo complete EMT. Tumor budding, long known to predict poor prognosis in CRC, is likely to be made of clusters of cells that are undergoing partial EMT. The mechanistic underpinnings and signaling pathways for such a complex process need to be understood better for more effective therapeutic interventions.
The aim of the current Research Topic is to cover promising, recent, and novel research trends in the field of epithelial to mesenchymal plasticity in CRC. Areas to be covered in this Research Topic may include, but are not limited to:
· Transcriptional, post transcriptional and post translational regulation of expression of epithelial and mesenchymal markers.
· Mechanism and functional analysis of drug resistance and/or reversal of drug resistance in CRC cells undergoing partial EMT.
· Biomarkers that can predict the induction of partial EMT.
· Role of stressors such as nutrient restriction or hypoxia in the induction of partial EMT.
· Theoretical and computational models that help understand EM transition and plasticity.
