Metabolic Adaptations in Cancer Stem Cells

Abstract

Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with remarkable ability to initiate, propagate, and spread the malignant disease. In addition, they exhibit increased resistance to anticancer therapies, thereby contributing to disease relapse. CSCs are reported to be present in many tumor types such as melanoma, sarcoma, mammary tumors, colon cancer and other solid tumors. These cells from different tumors show unique energetic and metabolic pathways. For example, CSCs from one type of tumor may predominantly use aerobic glycolysis, while from another tumor type may utilize oxidative phosphorylation. Most commonly these cells use fatty acid oxidation and ketone bodies as the main source of energy production. CSCs have a remarkable ability to reprogram their metabolism in order to survive under adverse conditions such as hypoxia, acidosis, and starvation. There is increasing interest to identify molecular targets that can be utilized to kill CSCs and to control their growth. In this review, we discuss how an understanding of the unique metabolism of CSCs from different tumors can offer promising strategies for targeting CSCs and hence to prevent disease relapse and to treat the metastatic disease.

PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress

“…It is currently well-established that an altered metabolism is a hallmark of cancer cells compared to their normal counterparts [ 25 , 26 , 27 ], with particular emphasis on CSCs. Thus, understanding the distinctive metabolism of CSCs can offer promising strategies for targeting them and consequently preventing recurrence and metastasis [ 27 ]. However, how metabolic pathways are interconnected with oncogenic signaling remains mostly unexplored.…”

EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?

“…CSCs are cancer cell subpopulations endowed with great adaptive potential which allows them to survive therapy-induced stress and to drive tumor relapse and metastasis, as an effect of molecular adaptive processes fueling clonal rearrangements of cancer cell subpopulations. CSCs are characterized by the expression of stemness genes and detoxifying systems and by great metabolic plasticity [ 144 , 145 , 146 , 147 ]. Epithelial to mesenchymal (EMT) transition is believed to play a role in fueling the emergence of CSC subpopulations [ 148 ].…”

Small Heat Shock Proteins in Cancers: Functions and Therapeutic Potential for Cancer Therapy

“…Cancer stem cells (CSCs), also termed "tumor-initiating cells" (TICs) or "sphere-forming cells", are a small subpopulation of stem-cell-like cancer cells that present the stem cell property of self-renewal, generating differentiated tumor cells and resistance to radiochemotherapy [125]. CSCs have been isolated from numerous solid and liquid tumors, including but not limited to leukemia, brain, head and neck, lung, breast, liver, stomach, colon, pancreatic, prostate, ovary, and bladder cancers and mesothelioma [126].…”