Lactate: A Metabolic Driver in the Tumour Landscape. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Ippolito, Luigi; Morandi, Andrea; Giannoni, Elisa; Chiarugi, Paola
• Is Part Of: Trends in biochemical sciences. Volume 44:Issue 2(2019)
• Page Start: 153
• Page End: 166
• Publication Date: 2019-02
• Subjects: mitochondria -- tumour–stroma interplay -- tumour microenvironment -- tumour metabolism; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2018.10.011
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : The presence of lactate in human tumours has been long neglected, confined to the role of a waste product derived from glycolysis and as a biomarker of malignancy. More recently, lactate has been rediscovered as signalling molecule that plays important roles in the regulation of the metabolic pathways, the immune response, and cell-to-cell communication within the tumour microenvironment. This review examines recent discoveries about the functional role of lactate in shaping the behaviour and the phenotype of tumour and tumour-associated cells, and describes potential clinical approaches to target lactate transport and metabolism in tumours. Highlights: In a tumour environment, lactate is no longer considered as a waste product from fermentative cell metabolism but instead as a powerful molecule that affects the behaviour of each cell surrounding and recruited to the tumour. Lactate establishes metabolic coupling between cancer cells and non-malignant cells, or among cancer cells themselves, thereby sustaining tumour growth. Lactate plays a key role in dampening immunosurveillance mediated by a plethora of immune cells recruited to the tumour site. Environmental lactate triggers signalling activation according to the cell subtype and its specific transporters/receptors. Targeting lactate metabolism and transport is a promising approach for cancer therapeutics.