Institut de Génétique Moléculaire de Montpellier (IGMM) - UMR5535


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Home page > Research Groups > Urszula HIBNER - HCV and Cancer

Urszula HIBNER - HCV and Cancer

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third cause of cancer mortality worldwide. Because therapeutic options for its treatment remain very limited, there is an urgent need to better understand the disease in order to define novel targets that may lead to innovative treatments.

More than 80% of HCC are linked to viral infection. Today, 170 million people are infected by Hepatitis C virus (HCV) and are thus at risk of developing HCC. Although efficient antiviral treatments are available, their current use (which is restricted to developed countries) will not have an impact on HCC frequency for many years to come.

Our team has contributed to the understanding of the effects of HCV on liver carcinogenesis. We have notably studied the impact of viral proteins on apoptotic signaling, loss of epithelial cell polarity, EMT and pro-inflammatory signaling triggered by NS5B, the viral polymerase. Additionally, we have shown that metabolic alterations in both human and mouse livers are due to HCV protein activities. After having discovered that the viral proteins trigger Wnt/β-catenin signaling, we are now exploring its impact both on virus-infected cells and on the “bystander” non-infected hepatocytes.

The high adaptability to changes in microenvironment is the basis of cancer cell plasticity. We study the adaptive response of transformed hepatocytes to hypoxia, which constitutes a major selection pressure in solid tumours, including HCC. Hepatocytes are particularly sensitive to oxygen deprivation and rapidly trigger pro-apoptotic response when confronted with low oxygen supply. However, a minority of cells survive and adapt, a process often accompanied by acquisition of the capacity to migrate towards less hostile environments. We explore the roles of transcription factors that regulate the epithelial- mesenchymal transition (EMT) in the adaptation of cancer cells to hypoxic stress. Our work has highlighted cooperative effects between different cancer cell subclones that lead to increased survival of tumour cells.

The current understanding of cancer disease includes notions derived from Darwin’s Theory of Evolution, notably as it relates to tumour heterogeneity. This theory, initially introduced in 1976 by Nowell (Science, 194, 23-28) has gained considerable traction due to the impressive acceleration of data accumulation through the generalised use of NGS (next generation sequencing). HCC are particularly heterogeneous, not only among different patients, but also between distinct regions of the same tumour.

In order to investigate functional aspects of tumour heterogeneity, our team uses cellular and animal models. In particular, we have developed orthotopic xenografts of cells transformed by various combinations of oncogenes. The cells are labelled with fluorescent protein markers, allowing us to follow them in situ, as well as isolate and further analyse them ex vivo. These studies provide information on interactions between tumour sub-clone cell populations as well as those between the tumour and its microenvironment.

Our main collaborators :

Daniel Fisher, IGMM, Montpellier
Jean Christophe Andrau, IGMM, Montpellier
Edouard Bertrand et Marion Peter, IGMM, Montpellier
Pr Georges Pageaux, Service Hépato-gastroentérologie, CHU Montpellier
Dr Jeanne Ramos, Service Biopathologie, CHU Montpellier
Michael Hochberg, Robert Noble, Institut de Sciences de l’Evolution, Montpellier
Stéphane Ansieau, CRCL, Lyon
David Durantel, CRCL, Lyon
Philip Meuleman, Gent University, Belgique
Leila Akkari, NKI, Amsterdam, Pays Bas

Our work is financed by :

Alumni (non-exhaustive)

Delphine Haouzi (post doc)
Hervé Lerat (post doc)
Olivier Disson (PhD)
Olivier Zugasti (PhD)
Fabien Binamé (PhD)
Nicolas Floc’h (PhD)
Leila Akkari (PhD)
Jakub Kolodziejski (PhD)
Marie Moreau (post-doc)
Christophe Carenco (M2, interne médecine)
Yannick Simonin (MCU)
Serena Vegna (PhD)

Institut de Génétique Moléculaire de Montpellier
CNRS-UMR 5535 - 1919, Route de Mende - 34293 Montpellier  Cedex 5
(+33) 04 34 35 96 01