Redressal of the Molecular Mechanisms of Colon and Other Cancer Stem Cell Energetics/Oxidative Stress for Possible Translation

Abstract

Cancer cells exhibit the unique property of metabolic reprogramming to attune with the adverse conditions, as dictated by the tumor microenvironment (TME). Cancer stem cells (CSCs) represent a minor subpopulation of a heterogeneous tumor mass exhibiting stem-like properties and are considered the primary culprit of tumor recurrence, metastatic dissemination with high refractoriness to conventional therapeutic approaches. Here we review the unique metabolic approaches adopted by CSCs under varying conditions and the fundamental molecular mechanisms central to the cellular energetics of CSCs, with particular emphasis on colorectal CSCs. With the keywords cancer stem cells/cellular energetics OR cellular energetics/tumor-initiating cells, cancer stem cells/metabolic reprogramming OR colorectal CSCs/cellular energetics, we shortlisted and performed in-depth information analysis of 100 articles from the public databases namely Elsevier, Scopus, and PubMed. The study revealed that CSCs exhibit distinctive metabolic heterogeneity and maintain the cellular energetics either by displaying enhanced aerobic glycolytic metabolism with a corresponding reduction in mitochondrial activity or by favorably maintaining mitochondrial oxidative phosphorylation (OXPHOS). CSCs are extraordinarily resilient and exhibit the properties of chemo- and radioresistance, and the remarkable feature of metabolic reprogramming in response to external or internal cues adds up to the CSC’s refractoriness. Furthermore, eradicating CSCs by targeting cellular metabolism will propel the existing therapeutic regime forward, leading to the emergence of novel therapeutic strategies. Metabotyping is the process of grouping metabolically similar phenotypes. Here the authors have mentioned about demonstrating specific metabolic phenotypes arising after metabolic reprogramming in cancer stem cells and the word can be rewritten as metabotypes.KeywordsCancer stem cellsCellular energeticsTumor-initiating cellsMetabolic reprogrammingColorectal CSCs