Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy

Qian Xie, Yanli Su, Karl Dykema, Jennifer Johnson, Julie Koeman, Valeria De Giorgi, Alan Huang, Robert Schlegel, Curt Essenburg, Liang Kang, Keiichi Iwaya, Shuhji Seki, Sok Kean Khoo, Boheng Zhang, Franco Buonaguro, Francesco M. Marincola, Kyle Furge, George F. Vande Woude, Nariyoshi Shinomiya

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)247-260
Number of pages14
JournalGenes and Cancer
Volume4
Issue number7-8
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Hepatocyte Growth Factor
Hepatitis B virus
Hepatocellular Carcinoma
Therapeutics
Liver Regeneration
Hepatitis B
Neoplasms
Biomarkers
Clinical Trials
Viruses

Keywords

  • hepatitis B
  • hepatocellular carcinoma
  • hepatocyte growth factor
  • MET
  • targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy. / Xie, Qian; Su, Yanli; Dykema, Karl; Johnson, Jennifer; Koeman, Julie; De Giorgi, Valeria; Huang, Alan; Schlegel, Robert; Essenburg, Curt; Kang, Liang; Iwaya, Keiichi; Seki, Shuhji; Khoo, Sok Kean; Zhang, Boheng; Buonaguro, Franco; Marincola, Francesco M.; Furge, Kyle; Vande Woude, George F.; Shinomiya, Nariyoshi.

In: Genes and Cancer, Vol. 4, No. 7-8, 03.2013, p. 247-260.

Research output: Contribution to journalArticle

Xie, Q, Su, Y, Dykema, K, Johnson, J, Koeman, J, De Giorgi, V, Huang, A, Schlegel, R, Essenburg, C, Kang, L, Iwaya, K, Seki, S, Khoo, SK, Zhang, B, Buonaguro, F, Marincola, FM, Furge, K, Vande Woude, GF & Shinomiya, N 2013, 'Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy', Genes and Cancer, vol. 4, no. 7-8, pp. 247-260. https://doi.org/10.1177/1947601913501075
Xie, Qian ; Su, Yanli ; Dykema, Karl ; Johnson, Jennifer ; Koeman, Julie ; De Giorgi, Valeria ; Huang, Alan ; Schlegel, Robert ; Essenburg, Curt ; Kang, Liang ; Iwaya, Keiichi ; Seki, Shuhji ; Khoo, Sok Kean ; Zhang, Boheng ; Buonaguro, Franco ; Marincola, Francesco M. ; Furge, Kyle ; Vande Woude, George F. ; Shinomiya, Nariyoshi. / Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy. In: Genes and Cancer. 2013 ; Vol. 4, No. 7-8. pp. 247-260.
@article{5f082e9d02374e699403f7d8fb8a124b,
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.",
keywords = "hepatitis B, hepatocellular carcinoma, hepatocyte growth factor, MET, targeted therapy",
author = "Qian Xie and Yanli Su and Karl Dykema and Jennifer Johnson and Julie Koeman and {De Giorgi}, Valeria and Alan Huang and Robert Schlegel and Curt Essenburg and Liang Kang and Keiichi Iwaya and Shuhji Seki and Khoo, {Sok Kean} and Boheng Zhang and Franco Buonaguro and Marincola, {Francesco M.} and Kyle Furge and {Vande Woude}, {George F.} and Nariyoshi Shinomiya",
year = "2013",
month = "3",
doi = "10.1177/1947601913501075",
language = "English",
volume = "4",
pages = "247--260",
journal = "Genes and Cancer",
issn = "1947-6019",
publisher = "SAGE Publications Inc.",
number = "7-8",

}

TY - JOUR

T1 - Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy

AU - Xie, Qian

AU - Su, Yanli

AU - Dykema, Karl

AU - Johnson, Jennifer

AU - Koeman, Julie

AU - De Giorgi, Valeria

AU - Huang, Alan

AU - Schlegel, Robert

AU - Essenburg, Curt

AU - Kang, Liang

AU - Iwaya, Keiichi

AU - Seki, Shuhji

AU - Khoo, Sok Kean

AU - Zhang, Boheng

AU - Buonaguro, Franco

AU - Marincola, Francesco M.

AU - Furge, Kyle

AU - Vande Woude, George F.

AU - Shinomiya, Nariyoshi

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

KW - hepatitis B

KW - hepatocellular carcinoma

KW - hepatocyte growth factor

KW - MET

KW - targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=84887414585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887414585&partnerID=8YFLogxK

U2 - 10.1177/1947601913501075

DO - 10.1177/1947601913501075

M3 - Article

C2 - 24167653

AN - SCOPUS:84887414585

VL - 4

SP - 247

EP - 260

JO - Genes and Cancer

JF - Genes and Cancer

SN - 1947-6019

IS - 7-8

ER -