title: Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating.
abstract: Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular 'building blocks' to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention.
authors.affiliation: Cancer Metabolism Research Unit, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.|Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, UK.
authors.forename: Evdokia
authors.initials: E
authors.lastname: Michalopoulou
authors.affiliation: Cancer Metabolism Research Unit, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.|Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, UK.
authors.forename: Vinay
authors.initials: V
authors.lastname: Bulusu
authors.affiliation: Cancer Metabolism Research Unit, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.|Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, UK.
authors.forename: Jurre J
authors.initials: JJ
authors.lastname: Kamphorst
mesh_terms: D000818:Animals; D001343:Autophagy; D002455:Cell Division; D015687:Cell Hypoxia; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D055432:Metabolomics; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010873:Pinocytosis / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: D005227:Fatty Acids; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases