From gametogenesis and stem cells to cancer: common metabolic themes

• Published in: Human reproduction update 2014-11, Vol.20 (6), p.924-943
• Main Authors: Pereira, Sandro L, Rodrigues, Ana Sofia, Sousa, Maria Inês, Correia, Marcelo, Perestrelo, Tânia, Ramalho-Santos, João
• Format: Article
• Language: English
• Subjects: Cell Differentiation - physiology; Cell Transformation, Neoplastic; Embryonic Development - physiology; Energy Metabolism - physiology; Gametogenesis - physiology; Glycolysis - physiology; Humans; Metabolic Networks and Pathways; Mitochondria - physiology; Neoplasms; Oxidative Phosphorylation; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Spermatogenesis - physiology
• ISSN: 1355-4786; 1460-2369
• DOI: 10.1093/humupd/dmu034

Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes. A search of the scientific literature available in the PubMed/Medline was conducted for studies on metabolism and mitochondrial function related to gametogenesis, early development, stem cells and cancers in the reproductive system, notably breast, prostate, ovarian and testicular cancers. Both PSCs and some types of cancer cells, particularly reproductive cancers, were found to obtain energy mostly by glycolysis, often reducing mitochondrial activity and oxidative phosphorylation. This strategy links proliferating cells, allowing for the biosynthesis reactions necessary for cell division. Interventions that affect metabolic pathways, and force cells to change their preferences, can lead to shifts in cell status, increasing either pluripotency or differentiation of stem cells, and causing cancer cells to become more or less aggressive. Interestingly metabolic changes in many cases seemed to lead to cell transformation, not necessarily follow it, suggesting a direct role of metabolic choices in influencing the (epi)genetic program of different cell types. There are uncanny similarities between PSCs and cancer cells at the metabolic level. Furthermore, metabolism may also play a direct role in cell status and targeting metabolic pathways could therefore be a promising strategy for both the control of cancer cell proliferation and the regulation of stem cell physiology, in terms of manipulating stem cells toward relevant phenotypes that may be important for tissue engineering, or making cancer cells become less tumorigenic.