Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

De Francesco, EM; Sotgia, F; Lisanti, MP

Abstract

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly,
the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic
dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer.

Citation

De Francesco, E., Sotgia, F., & Lisanti, M. (2018). Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication. Biochemical Journal, 475(9), 1611-1634. https://doi.org/10.1042/BCJ20170164

• Journal Article Type: Article
• Acceptance Date: Apr 12, 2018
• Online Publication Date: May 9, 2018
• Publication Date: May 9, 2018
• Deposit Date: May 1, 2018
• Publicly Available Date: May 21, 2018
• Journal: Biochemical Journal
• Print ISSN: 0264-6021
• Publisher: Portland Press
• Volume: 475
• Issue: 9
• Pages: 1611-1634
• DOI: https://doi.org/10.1042/BCJ20170164
• Publisher URL: https://doi.org/10.1042/BCJ20170164
• Related Public URLs: http://www.biochemj.org/
• Additional Information: Projects : Donation