Role of Mitochondria in Cancer Stem Cell Resistance

Abstract

Cancer stem cells (CSC) are associated with the mechanisms of chemoresistance to different cytotoxic drugs or radiotherapy, as well as with tumor relapse and a poor prognosis. Various studies have shown that mitochondria play a central role in these processes because of the ability of this organelle to modify cell metabolism, allowing survival and avoiding apoptosis clearance of cancer cells. Thus, the whole mitochondrial cycle, from its biogenesis to its death, either by mitophagy or by apoptosis, can be targeted by different drugs to reduce mitochondrial fitness, allowing for a restored or increased sensitivity to chemotherapeutic drugs. Once mitochondrial misbalance is induced by a specific drug in any of the processes of mitochondrial metabolism, two elements are commonly boosted: an increment in reactive nitrogen/oxygen species and, subsequently, activation of the intrinsic apoptotic pathway.

MiRNA-mediated EMT and CSCs in cancer chemoresistance

“…CSCs are a small subpopulation of cancer cells with stem cell-like characteristics, including quiescence, selfrenew, and slow cell cycle. A growing number of studies indicate conventional chemotherapeutics mainly target the bulk non-CSCs population instead of the rare CSCs population that indeed cause the clinical relapse [22]. Mechanism explorations reveal that CSCs are resistant to chemotherapy owing to their quiescent state, increased drug efflux, and activate DNA repair [23].…”

The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

“…These characteristics of CSCs make them among the main failure factors of anticancer therapies. In fact, the ability of CSCs to evade programmed cell death leads to resistance to various chemotherapeutic agents, such as those used in leukemia, malignant melanoma, brain, head and neck cancers, and breast, colorectal, and pancreas tumors [ 51 , 57 , 58 , 59 ]. Furthermore, resistance to radiotherapy in brain and breast cancers has also been demonstrated.…”

“…Furthermore, MOMP can induce cell death in an independent caspase process [ 64 , 65 , 66 , 67 ]. However, in some tumors, such as breast [ 68 , 69 , 70 ], ovary, and skin cancers, it has been shown that CSCs can evade death upon mitochondrial dysfunction [ 57 ]. Numerous investigations in colon or breast cancer cells have highlighted a correlation between increased aggressiveness and nonlethal caspase activation [ 71 , 72 , 73 ].…”

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

“…Like HSCs, AML cells have unique mitochondrial and metabolic features with reliance on OXPHOS [ 158 ]. Recently, the mitochondrial transacylase tafazzin (TAZ) was demonstrated to regulate AML stemness by modulating intracellular levels of phospholipids [ 159 ]. This X-linked gene was identified by a clustered regulatory interspaced palindromic repeat (CRISPR) screen.…”