The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes.

Simple Summary: Intratumoral heterogeneity is considered the major cause of drug resistance and hence treatment failure in cancer patients. Tumor cells are known for their phenotypic plasticity that is the ability of a cell to reprogram and change its identity to eventually adopt multiple phenotypes...

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Publicado en:Cancers Vol. 12; no. 12; pp. 3674 - 3675
Autores principales: Hass, Ralf, von der Ohe, Juliane, Ungefroren, Hendrik
Formato: pictorial review Journal Article
Publicado: MDPI Dec2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2020
      vid: 12
      iid: 12
      pid: 97109
      pub: MDPI
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        10.3390/cancers12123674
        148537788
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        atl: The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes.
      aug:
        au:
          Hass, Ralf
          von der Ohe, Juliane
          Ungefroren, Hendrik
        affil: Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany
      sug:
        subj:
          Neoplasms Pathology
          Epithelial-Mesenchymal Transition
          Stem Cells Metabolism
          Drug Resistance, Neoplasm
          Phenotype
          Cell Differentiation
          Epigenomics
          Gene Expression
          Neoplasms Drug Therapy
          Antineoplastic Agents
      ab: Simple Summary: Intratumoral heterogeneity is considered the major cause of drug resistance and hence treatment failure in cancer patients. Tumor cells are known for their phenotypic plasticity that is the ability of a cell to reprogram and change its identity to eventually adopt multiple phenotypes. Tumor cell plasticity involves the reactivation of developmental programs, the acquisition of cancer stem cell properties and an enhanced potential for retro- or transdifferentiation. A well-known transdifferentiation mechanism is the process of epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and various signals from the tumor microenvironment (TME) in shaping a tumor cell's plasticity. The vulnerabilities exposed by cancer cells when residing in a plastic or stem-like state have the potential to be exploited therapeutically, i.e., by converting highly metastatic cells into less aggressive or even harmless postmitotic ones. Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer's resistance to therapy and deciphering its underlying mechanisms.
      pubtype: Academic Journal
      doctype:
        pictorial
        review
        Journal Article
      ougenre: Article
    language: English
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