Biology subjects

St-Pierre-Wijckmans, W.

Publications and source records attributed to St-Pierre-Wijckmans, W..

3 recordsLinked to original sources

bioRxiv2026

PTPRF is a stress responsive cytoskeletal checkpoint that coordinates metabolic adaptation in hepatocytes and β cells

Cytoskeletal remodeling is essential for adaptation to nutrient availability, yet how cells coordinate actin dynamics with glucose homeostasis in metabolic organs remains unclear. Here, we identify a pathway linking metabolic stress to actin reorganization in hepatocytes and pancreatic {beta} cells. This mechanism involves transcriptional repression of the receptor protein tyrosine phosphatase PTPRF by spliced XBP1, a key unfolded protein response factor. In hepatocytes, PTPRF loss under dietary stress enhances insulin signaling, increases mitochondrial respiration and reduces steatosis. Proteomic analyses show that PTPRF interacts with regulators of actin polymerization and cell junctions, and its deletion promotes actin filament organization, shifting metabolism toward oxidative pathways. In {beta} cells, PTPRF deficiency similarly enhances actin polymerization and augments glucose-stimulated insulin secretion in obesity. Collectively, these findings place PTPRF as a nutrient-responsive regulator of cytoskeletal remodeling that coordinates hepatic metabolism and {beta}-cell function, highlighting its potential as a therapeutic target for improving systemic glucose control.

physiology↗

bioRxiv2026

Loss of PTPRK in hepatocytes reduces steatosis and carcinogen-induced tumour development in obesity

Protein tyrosine phosphatases are crucial regulators of metabolism with specific roles in different tissues. To investigate hepatocyte-specific function of protein tyrosine phosphatase receptor type K (PTPRK), we generated mice carrying floxed Ptprk alleles and crossed them with Alb-Cre mice (Ptprk{Delta}Hep mice). Under chow feeding, Ptprk{Delta}Hepmice were largely comparable to littermate controls. In contrast, Ptprk{Delta}Hepmice fed a high-fat, high-fructose, high-cholesterol diet exhibited reduced steatosis, lower hepatic PPAR{gamma}, and blunted hepatocyte hypertrophy, accompanied by improved systemic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamps. We identified PTPRK-interacting proteins enriched for metabolic functions associated with glycolysis and lipid biosynthesis using pull downs from primary hepatocyte lysates. In line with these findings, Ptprk{Delta}Hep mice developed fewer tumours than controls in an obesity and carcinogen-induced hepatocellular carcinoma (HCC) model. Our data show that under nutrient excess PTPRK is functionally engaged in hepatocytes to support PPAR{gamma}-linked steatotic growth, insulin resistance, and tumour initiation, highlighting PTPRK as a potential therapeutic target in MASLD-associated HCC.

pathology↗

bioRxiv2025

Feeding induces c-Fos in hepatocytes contributing to hepatocellular carcinoma in obesity

The transcription factor c-Fos plays an important role in hepatic metabolism; however, its role in metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC) is unclear. Here, we show that hepatic c-Fos is induced by insulin after feeding and suppressed by glucagon during fasting in chow-fed mice. In lean mice, adenovirus-mediated c-Fos ectopic expression in the liver is sufficient to cause insulin resistance. In diet-induced obesity or after ectopic expression in hepatocytes, c-Fos promotes MASLD progression by altering PPAR signaling and fatty acid metabolism pathways. Mechanistically, c-Fos drives glycolysis, stress-associated MAPK, and insulin-related PI3K-Akt signaling, exacerbating metabolic dysregulation. In HCC, c-Fos expression correlates with PI3K-Akt, MAPK, and calcium signaling pathways activation. Moreover, c-Fos siRNA knockdown in human liver cancer cells reduces proliferation and increases apoptosis under lipotoxic or ER stress conditions. These findings identify c-Fos as a critical mediator of liver steatosis progression, linking hepatocyte signaling and metabolic reprogramming to liver dysfunction and tumorigenesis.

cancer biology↗