Abstract

Metastatic progression, including extravasation and micrometastatic outgrowth, is the main cause of cancer patient death. Recent studies suggest that cancer cells reprogram their metabolism to support increased proliferation through increased glycolysis and biosynthetic activities, including lipogenesis pathways. However, metabolic changes during metastatic progression, including alterations in regulatory gene expression, remain undefined. We show that transforming growth factor beta 1 (TGFβ1)-induced epithelial-to-mesenchymal transition (EMT) is accompanied by coordinately reduced enzyme expression required to convert glucose into fatty acids, and concomitant enhanced respiration. Overexpressed Snail1, a transcription factor mediating TGFβ1-induced EMT, was sufficient to suppress carbohydrate-responsive-element-binding protein (ChREBP, a master lipogenic regulator), and fatty acid synthase (FASN), its effector lipogenic gene. Stable FASN knockdown was sufficient to induce EMT, stimulate migration and extravasation in vitro. FASN silencing enhanced lung metastasis and death in vivo. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGFβ1-induced EMT and metastasis.Oncogene advance online publication, 6 October 2014; doi:10.1038/onc.2014.321.

Original languageEnglish (US)
JournalOncogene
DOIs
StateAccepted/In press - Oct 6 2014

Fingerprint

Epithelial-Mesenchymal Transition
Fatty Acid Synthases
Transforming Growth Factor beta
Lipogenesis
Neoplasm Metastasis
Glycolysis
Regulator Genes
Oncogenes
Publications
Neoplasms
Carrier Proteins
Respiration
Transcription Factors
Fatty Acids
Carbohydrates
Gene Expression
Glucose
Lung
Enzymes
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. / Jiang, L.; Xiao, L.; Sugiura, H.; Huang, X.; Ali, A.; Kuro-O, M.; DeBerardinis, R. J.; Boothman, D. A.

In: Oncogene, 06.10.2014.

Research output: Contribution to journalArticle

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abstract = "Metastatic progression, including extravasation and micrometastatic outgrowth, is the main cause of cancer patient death. Recent studies suggest that cancer cells reprogram their metabolism to support increased proliferation through increased glycolysis and biosynthetic activities, including lipogenesis pathways. However, metabolic changes during metastatic progression, including alterations in regulatory gene expression, remain undefined. We show that transforming growth factor beta 1 (TGFβ1)-induced epithelial-to-mesenchymal transition (EMT) is accompanied by coordinately reduced enzyme expression required to convert glucose into fatty acids, and concomitant enhanced respiration. Overexpressed Snail1, a transcription factor mediating TGFβ1-induced EMT, was sufficient to suppress carbohydrate-responsive-element-binding protein (ChREBP, a master lipogenic regulator), and fatty acid synthase (FASN), its effector lipogenic gene. Stable FASN knockdown was sufficient to induce EMT, stimulate migration and extravasation in vitro. FASN silencing enhanced lung metastasis and death in vivo. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGFβ1-induced EMT and metastasis.Oncogene advance online publication, 6 October 2014; doi:10.1038/onc.2014.321.",
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AU - Xiao, L.

AU - Sugiura, H.

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AU - Ali, A.

AU - Kuro-O, M.

AU - DeBerardinis, R. J.

AU - Boothman, D. A.

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