NIS & Signalisation oncogénique

Equipe

Responsable : Jamila FAIVRE, MCU-PH

Marion DARNAUD, Ingénieur de Recherche

François FAITOT, Etudiant en Master

Fataneh FATEMI, Etudiante en Master

Michèle GIGOU, Assistant-Ingénieur

Claire LACOSTE, Ingénieur de recherche, Doctorante

Nicolas MONIAUX, Chargé de recherche Inserm

Haiyan SONG, Post-doctorante

Eric VIBERT, Chirurgien, Doctorant

Thématique de recherche

The aim of the research program “Primary Liver Cancer” is to characterize molecular signatures specific for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), gain insight into the biological activities linked to new oncogenic pathways related, or not, to HBV or HCV infections, and develop therapeutic and diagnostic innovations based on our experimental findings.

The project focuses on the functions of the Sodium Iodide Symporter (NIS, encoded by the SLC5A5 gene) in the liver. NIS has long been known for its physiological role in iodide thyroid transport, which is part of the biosynthetic process of thyroid hormones. More recently, NIS was found to be expressed in a series of normal or tumor extra thyroidal tissues, and has aroused interest because of its remarkable properties as a therapeutic (131I radiotherapy of non-thyroid cancers) and a reporter (nuclear imaging) gene. The functional role of NIS in extra thyroidal tissues is not yet known, except in the lactating mammary gland. During the 2006-2008 period, our team obtained a series of important results about the biological activity of hepatic NIS. We evidenced an overexpression of NIS in primary liver cancer, and proposed to investigate the hepatic expression profile, regulation and functions of NIS in order to disclose the extra-thyroidal activity of NIS, if any. We showed, among other things, that NIS was upregulated in human cholangiocarcinoma, was activated as from the preneoplastic stages of an experimental primary liver cancer (diethylnitrosamine-induced HCC in Wistar rats), and was maintained throughout the subsequent clonal expansion of cancer, accounting for the observed efficacy of 131I therapy applied at an early stage of the disease. This opened a new prospect for the radiotherapy of primary liver cancer and raised the question of whether the precocious NIS expressing cells were progenitor tumor cells (Liu et al. Gastroenterology 2007). Moreover, we found that NIS is expressed in biliary cells of normal liver. The expression is located in bile ducts and in the ductular cells of the Hering ducts, which constitute the hepatic stem cell compartment.

Globally, our researches have put NIS in a completely different perspective regarding its biological role in non thyroid epithelial cells. We are continuing the investigation of NIS properties along the following lines: (i) the hepatic transcriptional regulation of the gene NIS/SLC5A5; (ii) the role of NIS in cell migration; (iii) the role of NIS and cell polarization.