The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Oct 1

PMID 32998263

Citations 24

Authors

Atsushi Tanabe

Hiroeki Sahara

Affiliations

Soon will be listed here.

Abstract

Numerous findings have indicated that CSCs, which are present at a low frequency inside primary tumors, are the main cause of therapy resistance and cancer recurrence. Although various therapeutic methods targeting CSCs have been attempted for eliminating cancer cells completely, the complicated characteristics of CSCs have hampered such attempts. In analyzing the biological properties of CSCs, it was revealed that CSCs have a peculiar metabolism that is distinct from non-CSCs to maintain their stemness properties. The CSC metabolism involves not only the catabolic and anabolic pathways, but also intracellular signaling, gene expression, and redox balance. In addition, CSCs can reprogram their metabolism to flexibly respond to environmental changes. In this review, we focus on the flexible metabolic mechanisms of CSCs, and highlight the new therapeutics that target CSC metabolism.

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References

He T, Zhang Y, Jiang H, Li X, Zhu H, Zheng K . The c-Myc-LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol. 2015; 32(7):187. PMC: 4452209. DOI: 10.1007/s12032-015-0633-8. View

Lagadinou E, Sach A, Callahan K, Rossi R, Neering S, Minhajuddin M . BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013; 12(3):329-41. PMC: 3595363. DOI: 10.1016/j.stem.2012.12.013. View

De Francesco E, Ozsvari B, Sotgia F, Lisanti M . Dodecyl-TPP Targets Mitochondria and Potently Eradicates Cancer Stem Cells (CSCs): Synergy With FDA-Approved Drugs and Natural Compounds (Vitamin C and Berberine). Front Oncol. 2019; 9:615. PMC: 6692486. DOI: 10.3389/fonc.2019.00615. View

Viale A, Pettazzoni P, Lyssiotis C, Ying H, Sanchez N, Marchesini M . Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514(7524):628-32. PMC: 4376130. DOI: 10.1038/nature13611. View

Sinkala M, Mulder N, Martin D . Metabolic gene alterations impact the clinical aggressiveness and drug responses of 32 human cancers. Commun Biol. 2019; 2:414. PMC: 6856368. DOI: 10.1038/s42003-019-0666-1. View

Maddocks O, Berkers C, Mason S, Zheng L, Blyth K, Gottlieb E . Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2012; 493(7433):542-6. PMC: 6485472. DOI: 10.1038/nature11743. View

Eales K, Hollinshead K, Tennant D . Hypoxia and metabolic adaptation of cancer cells. Oncogenesis. 2016; 5:e190. PMC: 4728679. DOI: 10.1038/oncsis.2015.50. View

Warburg O, Wind F, Negelein E . THE METABOLISM OF TUMORS IN THE BODY. J Gen Physiol. 2009; 8(6):519-30. PMC: 2140820. DOI: 10.1085/jgp.8.6.519. View

Hawkins K, Joy S, Delhove J, Kotiadis V, Fernandez E, FitzPatrick L . NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming. Cell Rep. 2016; 14(8):1883-91. PMC: 4785773. DOI: 10.1016/j.celrep.2016.02.003. View

10.

Weber D, Aminazdeh-Gohari S, Kofler B . Ketogenic diet in cancer therapy. Aging (Albany NY). 2018; 10(2):164-165. PMC: 5842847. DOI: 10.18632/aging.101382. View

11.

Ubhi T, Brown G . Exploiting DNA Replication Stress for Cancer Treatment. Cancer Res. 2019; 79(8):1730-1739. DOI: 10.1158/0008-5472.CAN-18-3631. View

12.

Patra K, Hay N . The pentose phosphate pathway and cancer. Trends Biochem Sci. 2014; 39(8):347-54. PMC: 4329227. DOI: 10.1016/j.tibs.2014.06.005. View

13.

Sharick J, Walsh C, Sprackling C, Pasch C, Pham D, Esbona K . Metabolic Heterogeneity in Patient Tumor-Derived Organoids by Primary Site and Drug Treatment. Front Oncol. 2020; 10:553. PMC: 7242740. DOI: 10.3389/fonc.2020.00553. View

14.

Shyh-Chang N, Zhu H, de Soysa T, Shinoda G, Seligson M, Tsanov K . Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell. 2013; 155(4):778-92. PMC: 3917449. DOI: 10.1016/j.cell.2013.09.059. View

15.

Tan Z, Luo X, Xiao L, Tang M, Bode A, Dong Z . The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications. Mol Cancer Ther. 2016; 15(5):774-82. DOI: 10.1158/1535-7163.MCT-15-0621. View

16.

Liu K, Lee J, Kim J, Wang L, Tian Y, Chan S . Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells. Mol Cell. 2017; 68(2):281-292.e5. PMC: 5687282. DOI: 10.1016/j.molcel.2017.09.022. View

17.

Contractor T, Harris C . p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer Res. 2011; 72(2):560-7. DOI: 10.1158/0008-5472.CAN-11-1215. View

18.

Hayashi K, Jutabha P, Endou H, Anzai N . c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncol Rep. 2012; 28(3):862-6. DOI: 10.3892/or.2012.1878. View

19.

Cruz-Gil S, Sanchez-Martinez R, Wagner-Reguero S, Stange D, Scholch S, Pape K . A more physiological approach to lipid metabolism alterations in cancer: CRC-like organoids assessment. PLoS One. 2019; 14(7):e0219944. PMC: 6655698. DOI: 10.1371/journal.pone.0219944. View

20.

Wang C, Shao L, Pan C, Ye J, Ding Z, Wu J . Elevated level of mitochondrial reactive oxygen species via fatty acid β-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition. Stem Cell Res Ther. 2019; 10(1):175. PMC: 6567550. DOI: 10.1186/s13287-019-1265-2. View