Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Forum on Immunopathological Diseases and Therapeutics
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v2.i2.110
pages 195-204

Role of Raf Kinase Inhibitor Protein in Hepatocellular Carcinoma

Evan J. Walker
Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
Stephen A. Rosenberg
Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
Jack R. Wands
Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA
Miran Kim
Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA

ABSTRACT

Hepatocellular carcinoma (HCC) accounts for 80−90% of primary liver tumors and is one of the most common and devastating malignant diseases worldwide. The MAPK signaling pathway is activated in over 90% of HCCs, and RKIP has been identified as an inhibitor of the MAPK pathway. It has been observed that downregulation of RKIP expression in HCC tumors contributes to constitutive activation of the ERK/MAPK pathway and promotes proliferation and migration of HCC cells. More important, activation of IGF-I/ERK/MAPK pathways can be blocked by restoration of RKIP levels. The protein levels of RKIP are significantly reduced in HCC, whereas mRNA levels only decreased in 41% of HCC samples studied, suggesting that the downregulation of RKIP in HCC may be influenced through multiple mechanisms both at the mRNA and protein levels. In this context, mTOR inhibitor, insulin, and proteasome inhibitors were found to modulate RKIP expression in FOCUS HCC cells. A better understating of mechanisms by which RKIP expression is downregulated in HCC may be critical to develop a possible target for therapeutic intervention of HCC.


Articles with similar content:

Inhibition of Epithelial-to-Mesenchymal Transition (EMT) in Cancer by Nitric Oxide: Pivotal Roles of Nitrosylation of NF-κB, YY1 and Snail
Forum on Immunopathological Diseases and Therapeutics, Vol.3, 2012, issue 2
Stavroula Baritaki, Benjamin Bonavida
The EMT Universe: Space between Cancer Cell Dissemination and Metastasis Initiation
Critical Reviews™ in Oncogenesis, Vol.19, 2014, issue 5
Luigi Ombrato, Ilaria Malanchi
Yin Yang 1 and raf-1 Kinase Inhibitory Protein Status in Hepatocellular carcinoma: Future Perspectives
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 1-2
Luigi Inguglia, Melchiorre Cervello, Manuela Labbozzetta, Giuseppe Montalto, Rossana Porcasi, Lydia Giannitrapani, Paola Poma, Monica Notarbartolo, Natale D'Alessandro, Ada Maria Florena
Role of Raf Kinase Inhibitor Protein in Pathophysiology of Prostate Cancer
Forum on Immunopathological Diseases and Therapeutics, Vol.2, 2011, issue 1
Evan T. Keller
The Activated NF-κB-Snail-RKIP Circuitry in Cancer Regulates Both the Metastatic Cascade and Resistance to Apoptosis by Cytotoxic Drugs
Critical Reviews™ in Immunology, Vol.29, 2009, issue 3
Katherine Wu, Benjamin Bonavida