Metastasis is the major cause of death in cancer patients. Epithelial-mesenchymal transition (EMT) is a physiological process, during which epithelial cells transdifferentiate into mesenchymal ones. It is present during embryonic development, tissue repair, or wound healing. In cancer, EMT is considered the initial step of metastasis during which epithelial cells lose polarity, detach from the tumor tissue, and start to migrate. While EMT initiates and enables the metastatic cascade, its reverse process, mesenchymal-epithelial transition (MET), has been proposed as a necessary step for colonization and development of distant metastases.
Although the EMT is undoubtedly a conserved program under physiological conditions, we presume variations depending on the type of cell/tissue, type of pathology, oncogenic drivers, or epigenetic alterations. Thus far, several signaling pathways are known to facilitate the transition towards the mesenchymal phenotype (signaling via TGF-ß, RAS/MEK/ERK, WNT, NOTCH, HIFs, etc.), each of which has been earlier demonstrated to control cancer-specific metabolic changes. On the other hand, several lines of evidence point out that metabolic pathways in cancer support invasive phenotype. However, it needs to be clarified what mechanisms are involved in EMT regulation by means of metabolic reprogramming and if general oncogenic signaling drives metabolic changes along with EMT. In this respect, further evidence is needed to conclude on the causality of the EMT-induced metabolic remodeling and/or metabolism-induced EMT processes.
In addition to metastable properties, the mesenchymal phenotype bears an undefined degree of multipotency. Since cancer stem cells (CSC) are characterized by specific metabolic features, we should consider if the knowledge gathered in the field of CSC is applicable also to the mesenchymal phenotype at the metabolic level. Nowadays, EMT and embryonic/cancer stem cells are studied alongside.
From a practical viewpoint, there are several widely used markers of epithelial vs. mesenchymal phenotype in a laboratory environment. Nevertheless, the scientific community would benefit from additional novel approaches that would enable evaluating the degree of the EMT and defined cell/animal models to boost the studies on the mechanism of EMT in cancer etiology. Moreover, improved detection and quantification of EMT would benefit also the clinical environment.
This Research Topic will focus on the metabolic features accompanying EMT, and aims to gather current research on metabolic and genetic aspects of EMT in cancer, with an emphasis on the cancer histology and tissue-specific differences, including opinion on methodological aspects that facilitate EMT and MET studies in cancer etiology. The Research Topic welcomes Original and Review articles focusing on metabolic hallmarks associated with the EMT phenotype, such as:
1) Novel metabolic pathways promoting the metastatic potential of cancer cells;
2) Extrinsic and intrinsic signals promoting EMT and MET;
3) Use of EMT-related metabolic biomarkers in cancer diagnosis or treatment;
4) Tissue-specific differences of the EMT phenotype;
5) Methods and models for detection of the EMT in a laboratory environment;
6) EMT vs. cancer stem-like cell phenotype.
Metastasis is the major cause of death in cancer patients. Epithelial-mesenchymal transition (EMT) is a physiological process, during which epithelial cells transdifferentiate into mesenchymal ones. It is present during embryonic development, tissue repair, or wound healing. In cancer, EMT is considered the initial step of metastasis during which epithelial cells lose polarity, detach from the tumor tissue, and start to migrate. While EMT initiates and enables the metastatic cascade, its reverse process, mesenchymal-epithelial transition (MET), has been proposed as a necessary step for colonization and development of distant metastases.
Although the EMT is undoubtedly a conserved program under physiological conditions, we presume variations depending on the type of cell/tissue, type of pathology, oncogenic drivers, or epigenetic alterations. Thus far, several signaling pathways are known to facilitate the transition towards the mesenchymal phenotype (signaling via TGF-ß, RAS/MEK/ERK, WNT, NOTCH, HIFs, etc.), each of which has been earlier demonstrated to control cancer-specific metabolic changes. On the other hand, several lines of evidence point out that metabolic pathways in cancer support invasive phenotype. However, it needs to be clarified what mechanisms are involved in EMT regulation by means of metabolic reprogramming and if general oncogenic signaling drives metabolic changes along with EMT. In this respect, further evidence is needed to conclude on the causality of the EMT-induced metabolic remodeling and/or metabolism-induced EMT processes.
In addition to metastable properties, the mesenchymal phenotype bears an undefined degree of multipotency. Since cancer stem cells (CSC) are characterized by specific metabolic features, we should consider if the knowledge gathered in the field of CSC is applicable also to the mesenchymal phenotype at the metabolic level. Nowadays, EMT and embryonic/cancer stem cells are studied alongside.
From a practical viewpoint, there are several widely used markers of epithelial vs. mesenchymal phenotype in a laboratory environment. Nevertheless, the scientific community would benefit from additional novel approaches that would enable evaluating the degree of the EMT and defined cell/animal models to boost the studies on the mechanism of EMT in cancer etiology. Moreover, improved detection and quantification of EMT would benefit also the clinical environment.
This Research Topic will focus on the metabolic features accompanying EMT, and aims to gather current research on metabolic and genetic aspects of EMT in cancer, with an emphasis on the cancer histology and tissue-specific differences, including opinion on methodological aspects that facilitate EMT and MET studies in cancer etiology. The Research Topic welcomes Original and Review articles focusing on metabolic hallmarks associated with the EMT phenotype, such as:
1) Novel metabolic pathways promoting the metastatic potential of cancer cells;
2) Extrinsic and intrinsic signals promoting EMT and MET;
3) Use of EMT-related metabolic biomarkers in cancer diagnosis or treatment;
4) Tissue-specific differences of the EMT phenotype;
5) Methods and models for detection of the EMT in a laboratory environment;
6) EMT vs. cancer stem-like cell phenotype.
