Adult and Cancer Stem Cells: Perspectives on Autophagic Fate Determinations and Molecular Intervention
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Autophagy is a highly conserved mechanism for the maintenance of cellular homeostasis and functionality in pluripotent stem cells, adult stem cells, and normal somatic cells. Cytoprotective roles of autophagy are essential for eliminating damaged subcellular organelles like mitochondria and protein aggregates, thereby reducing reactive oxygen species (ROS) levels and promoting normal or cancer cell survival. We clarify multiple autophagic inducers, default pathway sensors, and regulators in various stages of stem cells. Of note, with autophagy deficiency, there are two major autophagy-associated outcomes, including pro-autophagic cell survival and death. Clearly, the fates of autophagic determination are tightly regulated by their microenvironments, cell types, and the interplay among multiple cell death machineries related to autophagy, apoptosis, and necrosis. Based on the above fundamental autophagic differences among various cell types, we propose a new concept, balanced autophagy, which sheds light on an equilibrium state between pro-autophagic cell survival and death. We further suggest new strategies targeting therapeutic-resistant cancer stem cells that emphasize the modulatory effects of pro-autophagic cell death in intractable cancer cells.
KeywordsAutophagy Mitophagy Adult stem cells Cancer stem cells Mitochondria
We would like to thank our colleague Professor R. Padmanabhan for discussion and Ms. Verma Walker, NIH Library Editing Service, for reviewing the manuscript.
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