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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2017; 23(24): 4330-4340
Published online Jun 28, 2017. doi: 10.3748/wjg.v23.i24.4330
Implication of the Hedgehog pathway in hepatocellular carcinoma
Carminia Maria Della Corte, Giuseppe Viscardi, Federica Papaccio, Giovanna Esposito, Giulia Martini, Davide Ciardiello, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo
Carminia Maria Della Corte, Giuseppe Viscardi, Federica Papaccio, Giovanna Esposito, Giulia Martini, Davide Ciardiello, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara”, Università degli studi della Campania “Luigi Vanvitelli”, 80131 Naples, Italy
Author contributions: Della Corte CM conducted data research and wrote the paper; Viscardi G, Papaccio F, Esposito G, Ciardiello D and Martinelli E conducted data research; Ciardiello F and Morgillo F contributed critical revision of the manuscript for important intellectual content.
Conflict-of-interest statement: Authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Floriana Morgillo, MD, PhD, Assistant Professor, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara”, Università degli studi della Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131 Naples, Italy. florianamorgillo@yahoo.com
Telephone: +39-81-5666628 Fax: +39-81-5666785
Received: February 7, 2017
Peer-review started: February 10, 2017
First decision: March 16, 2017
Revised: April 13, 2017
Accepted: May 19, 2017
Article in press: May 19, 2017
Published online: June 28, 2017
Processing time: 148 Days and 6.2 Hours
Abstract

The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma (HCC) is poor because there are few treatment options. Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis, proliferation and progression of HCC. Among all of the pathways that are involved in the development of HCC, Hedgehog (HH) signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression. HH plays a physiological role in embryogenesis, through the induction of the differentiation of hepatocytes from endodermal progenitors. The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development. HH activation sustains the sub-population of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC, and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells. High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome. In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth, metastasis and a mesenchymal phenotype.

Keywords: Hedgehog; Epithelial-mesenchymal transition; Hepatocellular carcinoma; Hepatocarcinogenesis; Prognosis

Core tip: The hedgehog (HH) pathway is involved in the embryonic development of liver, and its reactivation plays a substantial role in sustaining cancer cell growth and progression in hepatocellular carcinoma (HCC). In hepatocarcinogenesis, HH signalling is required for differentiation, proliferation and polarity of liver embryonic cells. High levels of expression of HH components in HCC tissues correlate with mesenchymal properties and maintain the proliferation of cancer stem cells, which is a dynamic source of malignant cells in HCC progression. Current data on HH inhibition in preclinical models further confirm the role of HH and deserve future investigations in a clinical setting.