title: Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy with dismal prognosis. Metastatic spread and therapeutic resistance, the main causes of PDAC-related mortalities, are both partially underlined by the epithelial-mesenchymal transition (EMT) of PDAC cells. While the role of Warburg metabolism has been recognized in supporting rapid cellular growth and proliferation in many cancer types, less is known about the metabolic changes occurring during EMT, particularly in the context of PDAC.
  
  
  RESULTS
  In the current study, experimental models of EMT were established in the Panc-1 cell line of human PDAC via exposure to two physiologically relevant EMT inducers (tumor necrosis factor-α and transforming growth factor-β) and the metabolic consequences examined. The two EMT models displayed similar alterations in the general metabolic profile including augmented glucose uptake and lactate secretion as well as the lack of change in oxidative metabolism. Examination of molecular markers revealed differences in the pathways underlying the metabolic rewiring.13C-Glucose tracer data confirmed that a major portion of accumulated lactate was derived from glucose, but subsequent flux analysis suggested involvement of non-canonical pathways towards lactate production.
  
  
  CONCLUSIONS
  Our results characterize the metabolic reprogramming occurring during PDAC cell EMT and highlight the common changes of increased glucose uptake and lactate secretion under different EMT conditions. Such insight is urgently required for designing metabolic strategies to selectively target cells undergoing EMT in PDAC.
authors: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW Australia.
authors: Menghan
authors: M
authors: Liu
authors: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW Australia ; Charles Perkins Centre, School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Lake-Ee
authors: LE
authors: Quek
authors: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW Australia.
authors: Ghazal
authors: G
authors: Sultani
authors: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW Australia.
authors: Nigel
authors: 0000-0002-0119-9328
authors: N
authors: Turner
keywords: 13C Metabolomics; Epithelial-mesenchymal transition; Glucose metabolism; Pancreatic adenocarcinoma; Tumor metabolism