title: The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming.
abstract: Tumorigenesis is often accompanied by metabolic changes that favor rapid energy production and increased biosynthetic capabilities. These metabolic adaptations promote the survival and proliferation of tumor cells, and in conjunction with the hypoxic and metabolically challenged tumor microenvironment, influence autophagic activity. Autophagy is a catabolic process that allows cellular macromolecules to be broken down and re-utilized as metabolic precursors. Stimulation of autophagy promotes the survival of tumor cells under stressful metabolic and environmental conditions, and counters the potentially deleterious effects of mitochondrial dysfunction and the ROS that these organelles generate. However, inhibition of autophagy has also been reported to fuel tumorigenesis. In spite of the advances in our understanding of the relationship between autophagy and tumorigenesis, it remains unclear whether the therapeutic approaches targeting autophagy should aim to increase or decrease autophagic flux in tumor tissues in human patients. Here, we review how metabolic reprogramming influences autophagic activity in tumors, and discuss how inhibition of autophagy might be exploited to target tumor cells that show altered metabolism.
authors.affiliation: Pfizer Oncology Research Unit, Pearl River, NY 10965, USA. christina.eng@pfizer.com
authors.forename: C H
authors.initials: CH
authors.lastname: Eng
authors.forename: R T
authors.initials: RT
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D015687:Cell Hypoxia; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D050155:Lipogenesis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D005973:Glutamine; D058570:TOR Serine-Threonine Kinases