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Cancers 2017, 9(6), 58; doi:10.3390/cancers9060058

The Therapeutic Targeting of HGF/c-Met Signaling in Hepatocellular Carcinoma: Alternative Approaches

1
Research Centre for Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
2
Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 970, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Jill M. Siegfried
Received: 3 March 2017 / Revised: 23 April 2017 / Accepted: 24 May 2017 / Published: 26 May 2017
(This article belongs to the Special Issue Hepatocyte Growth Factor Pathway in Cancer)
View Full-Text   |   Download PDF [558 KB, uploaded 31 May 2017]   |  

Abstract

The poor prognosis of hepatocellular carcinoma (HCC), one of the most devastating cancers worldwide, is due to frequent recurrence and metastasis. Among the metastatic factors in the tumor microenvironment, hepatocyte growth factor (HGF) has been well known to play critical roles in tumor progression, including HCC. Therefore, c-Met is now regarded as the most promising therapeutic target for the treatment of HCC. However, there are still concerns about resistance and the side effects of using conventional inhibitors of c-Met, such as tyrosine kinase inhibitors. Recently, many alternative strategies of c-Met targeting have been emerging. These include targeting the downstream effectors of c-Met, such as hydrogen peroxide-inducible clone 5 (Hic-5), to block the reactive oxygen species (ROS)-mediated signaling for HCC progression. Also, inhibition of endosomal regulators, such as PKCε and GGA3, may perturb the c-Met endosomal signaling for HCC cell migration. On the other hand, many herbal antagonists of c-Met-dependent signaling, such as saponin, resveratrol, and LZ-8, were identified. Taken together, it can be anticipated that more effective and safer c-Met targeting strategies for preventing HCC progression can be established in the future. View Full-Text
Keywords: hepatocellular carcinoma; metastasis; hepatocyte growth factor; c-Met; signaling transduction; therapeutic target hepatocellular carcinoma; metastasis; hepatocyte growth factor; c-Met; signaling transduction; therapeutic target
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Hu, C.-T.; Wu, J.-R.; Cheng, C.-C.; Wu, W.-S. The Therapeutic Targeting of HGF/c-Met Signaling in Hepatocellular Carcinoma: Alternative Approaches. Cancers 2017, 9, 58.

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