title: Neurotensin regulation induces overexpression and activation of EGFR in HCC and restores response to erlotinib and sorafenib.
abstract: Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer due to the combination of late diagnosis and a lack of curative treatments. The identification of factors which promote tumor aggressiveness, and those that predict treatment responses, are a means to optimize the management of HCC patients. The complex of Neurotensin (NTS) and its high affinity receptor (NTSR1) has been shown to induce tumor growth and metastasis process in various cancers. In this paper, we propose that NTS and NTSR1 can assist in the management of HCC. Concomitant expression of NTS/NTSR1 was correlated with poor prognosis and found in 50% of HCC patients. We show that NTSR1 expression was positively correlated with the alteration of the Wnt/β-catenin pathway. Its activation creates EGFR driver activation which consequently enhances tumor progression, and sensitizes HCC tumor cells to TKI, such as sorafenib. The NTS/NTSR1 complex is a potential drug target for HCC, because it is an upstream regulator in the chain of cellular events involved in HCC progression. It could also be used as a theranostic biomarker for sorafenib to improve the HCC patient management.
authors.affiliation: INSERM UMRS 1007, Université Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Zherui
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Biochemistry Department, Centre de Biologie Humaine (CBH), CHU Amiens Sud, 80054 Amiens, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
authors.affiliation: INSERM UMRS 1007, Université Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: INSERM UMRS 1007, Université Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stadler
authors.affiliation: Pathology Department AP-HP Hôpital Saint-Antoine, Sorbonne Universités, UPMC Univ Paris 06, UMR_S938, St Antoine Research Center, F-75012 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
authors.affiliation: INSERM UMRS 1007, Université Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Segal-Bendirdjian
authors.affiliation: Pathology Department CHU Beaujon, 92110 Clichy, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.affiliation: INSERM UMRS 1007, Université Paris Descartes, 75270 Paris Cedex 06, France. Electronic address: patricia.forgez@inserm.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Forgez
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D009496:Neurotensin / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D000077157:Sorafenib; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D009496:Neurotensin; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: Cancer progression; EGFR; Erlotinib; Hepatocellular carcinoma; Neurotensin; Sorafenib