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

被引:185
作者
de Francesco, Ernestina M. [1 ,2 ]
Sotgia, Federica [3 ]
Lisanti, Michael P. [3 ]
机构
[1] Univ Calabria, Dept Pharm Hlth & Nutr Sci, Arcavacata Di Rende, Italy
[2] Univ Manchester, Paterson Inst, Manchester, Lancs, England
[3] Univ Salford, Biomed Res Ctr, Sch Environm & Life Sci, Translat Med, Manchester, England
关键词
TUMOR-INITIATING CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL BIOGENESIS; CLONAL EVOLUTION; LUNG-CANCER; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; QUANTITATIVE PROTEOMICS; ALDEHYDE DEHYDROGENASE; THERAPEUTIC TARGETS;
D O I
10.1042/BCJ20170164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 repertoire 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, oncogenic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a consequence 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 biochemical 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.
引用
收藏
页码:1611 / 1634
页数:24
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