title: Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy.
abstract: Hepatitis B virus (HBV) is a well-known cause of hepatocellular carcinoma (HCC), but the regulators effectively driving virus production and HCC progression remain unclear. By using genetically engineered mouse models, we show that overexpression of hepatocyte growth factor (HGF) accelerated HCC progression, supporting the genomic analysis that an up-regulated HGF signature is associated with poor prognosis in HBV-positive HCC patients. We show that for both liver regeneration and spontaneous HCC development there is an inclusive requirement for MET expression, and when HGF induces autocrine activation the tumor displays sensitivity to a small-molecule Met inhibitor. Our results demonstrate that HGF is a driver of HBV-induced HCC progression and may serve as an effective biomarker for Met-targeted therapy. MET inhibitors are entering clinical trials against cancer, and our data provide a molecular basis for targeting the Met pathway in hepatitis B-induced HCC.
authors.affiliation: Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xie
authors.forename: Yanli
authors.initials: Y
authors.lastname: Su
authors.forename: Karl
authors.initials: K
authors.lastname: Dykema
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnson
authors.forename: Julie
authors.initials: J
authors.lastname: Koeman
authors.forename: Valeria
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Alan
authors.initials: A
authors.lastname: Huang
authors.forename: Robert
authors.initials: R
authors.lastname: Schlegel
authors.forename: Curt
authors.initials: C
authors.lastname: Essenburg
authors.forename: Liang
authors.initials: L
authors.lastname: Kang
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Sok Kean
authors.initials: SK
authors.lastname: Khoo
authors.forename: Boheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Franco
authors.initials: F
authors.lastname: Buonaguro
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: George F
authors.initials: GF
authors.lastname: Vande Woude
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
keywords: MET; hepatitis B; hepatocellular carcinoma; hepatocyte growth factor; targeted therapy