Oncogenic functions of β-catenin signaling in the liver (ONCOLIV)

Director : 

Sabine Colnot

Deputy Director : 

Angélique Gougelet

 

Primary liver cancer is the second cause of death related to cancer worldwide. Our objective is to unravel the sequence of the events driving liver carcinogenesis, to open new diagnostic and therapeutic opportunities. We focus on β-catenin pathway, driver in one third of hepatocellular carcinomas (HCC) in patients. We mainly based our approach using preclinical transgenic mouse models.

 

Scientific Themes

Mechanisms and consequences of β-catenin-dependent transcription in liver cancers

Assessing how β-catenin and epigenetics interact to control gene transcription in the hepatocyte Identifying functional consequences on tumor metabolism and epigenetics.

Oncogenic cooperations in β-catenin-dependent HCC

Assessing in vivo in transgenic mice the epistatic relationship between mutated drivers in β-catenin-dependent HCC.

Tumor metabolism in HCC

Identifying how metabolic alterations impact on β-catenin-dependent hepatocarcinogenesis, and using transgenic mice as preclinical models to assess their efficacy.

Main publications

Riou, R., Ladli, M., Gerbal-Chaloin, S., Bossard, P., Gougelet, A., Godard, C., Loesch, R., Lagoutte, I., Lager, F., Calderaro, J., Dos Santos, A., Wang, Z., Verdier, F., and Colnot, S. (2020). ARID1A loss in adult hepatocytes activates beta-catenin-mediated erythropoietin transcription. Elife 9.

Gougelet, A., Sartor, C., Senni, N., Calderaro, J., Fartoux, L., Lequoy, M., Wendum, D., Talbot, J.N., Prignon, A., Chalaye, J., Imbeaud, S., Zucman-Rossi, J., Tordjmann, T., Godard, C., Bossard, P., Rosmorduc, O., Amaddeo, G., and Colnot, S. (2019). Hepatocellular Carcinomas With Mutational Activation of Beta-Catenin Require Choline and Can Be Detected by Positron Emission Tomography. Gastroenterology 157, 807-822.

Benabou, E., Salame, Z., Wendum, D., Lequoy, M., Tahraoui, S., Merabtene, F., Chretien, Y., Scatton, O., Rosmorduc, O., Fouassier, L., Fartoux, L., Praz, F., and Desbois-Mouthon, C. (2019). Insulin receptor isoform A favors tumor progression in human hepatocellular carcinoma by increasing stem/progenitor cell features. Cancer Lett 450, 155-168.

Gougelet, A., Sartor, C., Bachelot, L., Godard, C., Marchiol, C., Renault, G., Tores, F., Nitschke, P., Cavard, C., Terris, B., Perret, C., and Colnot, S. (2016). Antitumour activity of an inhibitor of miR-34a in liver cancer with beta-catenin-mutations. Gut 65, 1024-1034.

Gougelet, A., Torre, C., Veber, P., Sartor, C., Bachelot, L., Denechaud, P.D., Godard, C., Moldes, M., Burnol, A.F., Dubuquoy, C., Terris, B., Guillonneau, F., Ye, T., Schwarz, M., Braeuning, A., Perret, C., and Colnot, S. (2014). T-cell factor 4 and beta-catenin chromatin occupancies pattern zonal liver metabolism in mice. Hepatology 59, 2344-2357.

Chettouh, H., Fartoux, L., Aoudjehane, L., Wendum, D., Claperon, A., Chretien, Y., Rey, C., Scatton, O., Soubrane, O., Conti, F., Praz, F., Housset, C., Rosmorduc, O., and Desbois-Mouthon, C. (2013). Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. Cancer Res 73, 3974-3986.

Torre, C., Benhamouche, S., Mitchell, C., Godard, C., Veber, P., Letourneur, F., Cagnard, N., Jacques, S., Finzi, L., Perret, C., and Colnot, S. (2011). The transforming growth factor-alpha and cyclin D1 genes are direct targets of beta-catenin signaling in hepatocyte proliferation. J Hepatol 55, 86-95.

Benhamouche, S., Decaens, T., Godard, C., Chambrey, R., Rickman, D.S., Moinard, C., Vasseur-Cognet, M., Kuo, C.J., Kahn, A., Perret, C., and Colnot, S. (2006). Apc tumor suppressor gene is the “zonation-keeper” of mouse liver. Dev Cell 10, 759-770.

Colnot, S., Decaens, T., Niwa-Kawakita, M., Godard, C., Hamard, G., Kahn, A., Giovannini, M., and Perret, C. (2004). Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas. Proc Natl Acad Sci U S A 101, 17216-17221.

All publications