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Biomedicines 2014, 2(4), 327-344; doi:10.3390/biomedicines2040327

HGF/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis

University of Hawai'i Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA
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Received: 30 September 2014 / Revised: 3 November 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
(This article belongs to the Special Issue New aspects of the Hepatocyte Growth Factor/c-Met System)
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Abstract

Malignant mesothelioma (MM) is a highly aggressive cancer related to asbestos or erionite exposure and resistant to current therapies. Hepatocyte Growth Factor (HGF) and its tyrosine kinase receptor Met regulate cell growth, survival, motility/migration, and invasion. HGF and Met are expressed in MM cells, suggesting that the HGF/Met signaling plays a role in development and progression of this tumor, by autocrine and/or paracrine mechanisms. Upregulation and ligand-independent activation of Met, which is under suppressive control of miR-34 family members, correlate with enhanced invasion, migration and metastatic potential in several cancers, including MM. Moreover, Simian Virus 40 (SV40) Tag expression also induces a HGF autocrine circuit in an Rb-dependent manner in human mesothelial cells (HM) and possibly other cell types, enhancing cell adhesion, invasion and angiogenesis. The resulting activation of Met causes HM transformation and cell cycle progression, and contributes to virus particle assembling and infection of adjacent cells. The constitutive activation of Met, frequently occurring in MM, has been successfully targeted in preclinical models of MM. In conclusion, Met expression, activation state, subcellular localization and also HGF co-receptors expression, such as CD44, have clinical relevance for novel targeted therapies in a cancer for which no effective treatment is currently available. View Full-Text
Keywords: malignant mesothelioma; asbestos; erionite; HGF; Met; Akt; SV40; epithelial-mesenchymal transition (EMT) malignant mesothelioma; asbestos; erionite; HGF; Met; Akt; SV40; epithelial-mesenchymal transition (EMT)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gaudino, G.; Yang, H.; Carbone, M. HGF/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis. Biomedicines 2014, 2, 327-344.

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