Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition

Area of Science:

• Cancer Biology
• Metabolic Reprogramming
• Metastasis Research

Background:

• Metastatic progression is the primary cause of cancer mortality.
• Cancer cells alter metabolism, favoring glycolysis and biosynthesis, but regulatory changes during metastasis are unclear.
• Transforming growth factor beta 1 (TGFβ1) induces epithelial-to-mesenchymal transition (EMT), a key process in metastasis.

Purpose of the Study:

• To define metabolic changes and regulatory gene expression during metastatic progression.
• To investigate the role of lipogenesis suppression in TGFβ1-induced EMT and metastasis.

Main Methods:

• Analyzed enzyme expression during TGFβ1-induced EMT.
• Investigated the effect of Snail1 overexpression on lipogenic regulators (ChREBP, FASN).
• Utilized stable FASN knockdown in vitro and in vivo models to assess EMT, migration, extravasation, and metastasis.

Main Results:

• TGFβ1-induced EMT reduced enzymes for glucose-to-fatty acid conversion and increased respiration.
• Snail1 suppressed ChREBP and FASN expression.
• FASN knockdown induced EMT, enhanced migration and extravasation in vitro, and increased lung metastasis and mortality in vivo.

Conclusions:

• A metabolic shift suppressing lipogenesis and favoring energy production is crucial for TGFβ1-induced EMT.
• This metabolic transition is an essential driver of cancer metastasis.
• Targeting lipogenesis pathways may offer novel therapeutic strategies for metastatic cancer.