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Snail1: A Transcriptional Factor Controlled at Multiple Levels
Open AccessArticle

Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells

1
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, 2052 NSW, Australia
2
Charles Perkins Centre, School of Mathematics and Statistics, The University of Sydney, Sydney, 2006 NSW, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(6), 822; https://doi.org/10.3390/jcm8060822
Received: 5 April 2019 / Revised: 5 June 2019 / Accepted: 5 June 2019 / Published: 8 June 2019
The zinc finger transcription factor Snail is a known effector of epithelial-to-mesenchymal transition (EMT), a process that underlies the enhanced invasiveness and chemoresistance of common to cancerous cells. Induction of Snail-driven EMT has also been shown to drive a range of pro-survival metabolic adaptations in different cancers. In the present study, we sought to determine the specific role that Snail has in driving EMT and adaptive metabolic programming in pancreatic ductal adenocarcinoma (PDAC) by overexpressing Snail in a PDAC cell line, Panc1, and in immortalized, non-tumorigenic human pancreatic ductal epithelial (HPDE) cells. Snail overexpression was able to induce EMT in both pancreatic cell lines through suppression of epithelial markers and upregulation of mesenchymal markers alongside changes in cell morphology and enhanced migratory capacity. Snail-overexpressed pancreatic cells additionally displayed increased glucose uptake and lactate production with concomitant reduction in oxidative metabolism measurements. Snail overexpression reduced maximal respiration in both Panc1 and HPDE cells, with further reductions seen in ATP production, spare respiratory capacity and non-mitochondrial respiration in Snail overexpressing Panc1 cells. Accordingly, lower expression of mitochondrial electron transport chain proteins was observed with Snail overexpression, particularly within Panc1 cells. Modelling of 13C metabolite flux within both cell lines revealed decreased carbon flux from glucose in the TCA cycle in snai1-overexpressing Panc1 cells only. This work further highlights the role that Snail plays in EMT and demonstrates its specific effects on metabolic reprogramming of glucose metabolism in PDAC. View Full-Text
Keywords: SNA1; metabolomics; glucose metabolism; tumor metabolism; epithelial-mesenchymal transition; pancreatic adenocarcinoma SNA1; metabolomics; glucose metabolism; tumor metabolism; epithelial-mesenchymal transition; pancreatic adenocarcinoma
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Liu, M.; Hancock, S.E.; Sultani, G.; Wilkins, B.P.; Ding, E.; Osborne, B.; Quek, L.-E.; Turner, N. Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells. J. Clin. Med. 2019, 8, 822.

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