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PDA (pancreatic ductal adenocarcinoma) targets

Victoire Gouirand

The EMBO Journal


PDA (Pancreatic ductal adenocarcinoma) tumor cells are privated of oxygen, many nutrients and c they must adapt the metabolism to control the proliferation.

This cancer born when the cells in the pancreas, a glandular organ behind the stomach, start to multiply out of control and form a mass.

In some physiological states, cells rely on ketone bodies to satisfy their metabolic needs, especially during nutrient stress.

We show that tumor cells can activate ketone body metabolism and β-hydroxybutyrate is an alternative cell-intrinsic or systemic fuel that can promote PDA growth.

Pancreatic ductal adenocarcinoma cells activate enzymes, using various nutrients as carbon sources for body formation.

By assessing metabolic gene expression from spontaneously arising Pancreatic ductal adenocarcinoma tumors in mice, we find HMG-CoA lyase, involved in ketogenesis, to be among the most deregulated metabolic enzymes in PDA compared to normal pancreas. 

In vitro depletion of HMGCL it prevents the migration, cells expansion, and anchorage-independent tumor sphere compaction.

Moreover, disrupting HMGCL drastically decreases Pancreatic ductal adenocarcinoma tumor growth in vivo, while βOHB stimulates metastatic dissemination to the liver.

These findings suggest that βOHB increases cancer aggressiveness and it identify HMGCL and ketogenesis as metabolic targets for limiting its progression.


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