Increased glycolysis and functional mitochondria fuel acinar-ductal metaplasia in the pancreas
Neuss, T.; Wirges, N.; Chen, M.-C.; Usluer, S.; Oellinger, R.; Lier, S.; Dudek, M.; Madl, T.; Jastroch, M.; Steiger, K.; Schmitz, W.; Einwaechter, H.; Schmid, R. M.
Show abstract
Reprogramming of the cellular metabolism is a hallmark of pancreatic cancer, yet it remains unclear at what stage during carcinogenesis it occurs. Here, we investigated the metabolic requirements for acinar-to-ductal metaplasia (ADM), the first step in pancreatic carcinogenesis. We detected increased glycolytic marker expression in human ADM suggesting that a metabolic switch occurs during ADM formation. We report that this switch was similarly required for ADM formation in different oncogenic mouse models (KRAS, PI3K, and MEK1) and in ligand-induced ADM in mouse wild-type acini. In addition, we show that a functional electron transport chain (ETC), but not mitochondrial ATP production, was essential to ADM formation. We conclude that the ETC provides NAD+ for the de novo synthesis of serine from glycolysis intermediates. Our findings demonstrate that metabolic programming is essential for the initiation of pancreatic carcinogenesis and thus identifies potential targets for metabolic intervention.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling 95%
- Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity 94%
- Genetic Impairment of Succinate Metabolism Disrupts Bioenergetic Sensing in Adrenal Neuroendocrine Cancer 94%
Similar papers in this journal
- Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state 94%
- Pyruvate kinase controls signal strength in the insulin secretory pathway 94%
- Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation 94%
Similar papers in this journal
- An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas 94%
- Jag1 modulates an oscillatory Dll1-Notch-Hes1 signaling module to coordinate growth and fate of pancreatic progenitors 94%
- A combined transcriptional and dynamic roadmap of single human pancreatic endocrine progenitors reveals proliferative capacity and differentiation continuum 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.