LECTURE SERIES – 15.01.2026
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SPEAKERS:
Hennequart
Professor of Biochemistry and Cell Biology at University of Namur, Belgium
One-carbon metabolism in pancreatic cancer
Abstract
Acinar-to-ductal metaplasia (ADM) contributes to pancreatic repair after injury. However, persistent ADM, combined with KRAS mutations, leads to the development of precancerous pancreatic intraepithelial neoplasia (PanINs) that can progress into pancreatic ductal adenocarcinoma (PDAC). While PDAC development is well documented, the metabolic rewiring that occurs during early events such as ADM is poorly understood. Here, we show that Aldehyde Dehydrogenase 1 Family Member L2 (ALDH1L2), an NADPH-producing mitochondrial enzyme of the one-carbon pathway, limits reactive oxygen species (ROS) and formate production in pancreatic acinar cells. However, ALDH1L2 expression decreases progressively during ADM and is completely absent in pancreatic ductal cells. ALDH1L2 loss elevates ROS and promotes ADM in a model of pancreatitis and accelerates tumor progression in models of pancreatic cancer. We also show that, as a result of ALDH1L2 loss, circulating formate increases during PDAC progression in mice and humans. Overall, our findings identify ROS as a driver of ADM and suggest that circulating formate may serve as a biomarker for PDAC progression.
Schulze
Division Head – German Cancer Research Center (DKFZ)
Metabolism of essential fatty acids is a driver of ferroptosis in VHL mutant renal cancer
Abstract
Cancer cells frequently show high sensitivity towards ferroptosis, a form of regulated cell death triggered by toxic accumulation of lipid hydroperoxides derived from lipids containing polyunsaturated fatty acids (PUFAs). Importantly, linoleic acid (LA) is the major omega-6 PUFA component of western diets and considered a risk factor for cancerdevelopment. Here we show that treatment with LA increases ferroptosis sensitivity in clear cell renal cell carcinoma (ccRCC) cells. This was associated with elevated production of PUFA-containing phospholipids, particularly plasmalogen-phosphatidylethanolamines(pPE) and diacyl-PUFA phosphatidylcholines (PC). Furthermore, we found that fatty acid desaturase 2 (FADS2) governs a critical step in LA metabolism that determines ferroptosis sensitivity in ccRCC cells. Finally, lipidomic analysis revealed that ccRCC tissue contains high levels of omega-6 PUFA, suggesting that FADS2 is active in these cancers. Our results suggest that LA metabolism via FADS2 is a major driver of ferroptosis sensitivity in ccRCC.
Host
Meiser
LOCATION
BAM
Room: Mc Clintock A & B
6A, rue Nicolas- Ernest Barblé
L-1210 Luxembourg
LECTURE: 10:00 am – 11:30 am
Webinar via Webex:
Event number: 2786 111 5674
Event password: grWHBDXK442
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