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RETRACTED ARTICLE

Role of hepatitis C virus induced osteopontin in epithelial to mesenchymal transition, migration and invasion of hepatocytes.
PLoS One 2014; 9(1):e87464Plos

Abstract

Osteopontin (OPN) is a secreted phosphoprotein which has been linked to tumor progression and metastasis in a variety of cancers including hepatocellular carcinoma (HCC). Previous studies have shown that OPN is upregulated during liver injury and inflammation. However, the role of OPN in hepatitis C virus (HCV)-induced liver disease pathogenesis is not known. In this study, we determined the induction of OPN, and then investigated the effect of secreted forms of OPN in epithelial to mesenchymal transition (EMT), migration and invasion of hepatocytes. We show the induction of OPN mRNA and protein expression by HCV-infection. Our results also demonstrate the processing of precursor OPN (75 kDa) into 55 kDa, 42 kDa and 36 kDa forms of OPN in HCV-infected cells. Furthermore, we show the binding of secreted OPN to integrin αVβ3 and CD44 at the cell surface, leading to the activation of downstream cellular kinases such as focal adhesion kinase (FAK), Src, and Akt. Importantly, our results show the reduced expression of epithelial marker (E-cadherin) and induction of mesenchymal marker (N-cadherin) in HCV-infected cells. We also show the migration and invasion of HCV-infected cells using wound healing assay and matrigel coated Boyden chamber. In addition, we demonstrate the activation of above EMT markers, and the critical players involved in OPN-mediated cell signaling cascade using primary human hepatocytes infected with Japanese fulminant hepatitis (JFH)-1 HCV. Taken together, these studies suggest a potential role of OPN in inducing chronic liver disease and HCC associated with chronic HCV infection.

Authors+Show Affiliations

Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, Illinois, United States of America.Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, Illinois, United States of America.Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, Illinois, United States of America.Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC, United States of America.Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, Illinois, United States of America.Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, Illinois, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Retracted Publication

Language

eng

PubMed ID

24498111

Citation

Iqbal, Jawed, et al. "Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes." PloS One, vol. 9, no. 1, 2014, pp. e87464.
Iqbal J, McRae S, Mai T, et al. Role of hepatitis C virus induced osteopontin in epithelial to mesenchymal transition, migration and invasion of hepatocytes. PLoS ONE. 2014;9(1):e87464.
Iqbal, J., McRae, S., Mai, T., Banaudha, K., Sarkar-Dutta, M., & Waris, G. (2014). Role of hepatitis C virus induced osteopontin in epithelial to mesenchymal transition, migration and invasion of hepatocytes. PloS One, 9(1), pp. e87464. doi:10.1371/journal.pone.0087464.
Iqbal J, et al. Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes. PLoS ONE. 2014;9(1):e87464. PubMed PMID: 24498111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of hepatitis C virus induced osteopontin in epithelial to mesenchymal transition, migration and invasion of hepatocytes. AU - Iqbal,Jawed, AU - McRae,Steven, AU - Mai,Thi, AU - Banaudha,Krishna, AU - Sarkar-Dutta,Mehuli, AU - Waris,Gulam, Y1 - 2014/01/31/ PY - 2013/11/11/received PY - 2013/12/26/accepted PY - 2014/2/6/entrez PY - 2014/2/6/pubmed PY - 2014/10/16/medline SP - e87464 EP - e87464 JF - PloS one JO - PLoS ONE VL - 9 IS - 1 N2 - Osteopontin (OPN) is a secreted phosphoprotein which has been linked to tumor progression and metastasis in a variety of cancers including hepatocellular carcinoma (HCC). Previous studies have shown that OPN is upregulated during liver injury and inflammation. However, the role of OPN in hepatitis C virus (HCV)-induced liver disease pathogenesis is not known. In this study, we determined the induction of OPN, and then investigated the effect of secreted forms of OPN in epithelial to mesenchymal transition (EMT), migration and invasion of hepatocytes. We show the induction of OPN mRNA and protein expression by HCV-infection. Our results also demonstrate the processing of precursor OPN (75 kDa) into 55 kDa, 42 kDa and 36 kDa forms of OPN in HCV-infected cells. Furthermore, we show the binding of secreted OPN to integrin αVβ3 and CD44 at the cell surface, leading to the activation of downstream cellular kinases such as focal adhesion kinase (FAK), Src, and Akt. Importantly, our results show the reduced expression of epithelial marker (E-cadherin) and induction of mesenchymal marker (N-cadherin) in HCV-infected cells. We also show the migration and invasion of HCV-infected cells using wound healing assay and matrigel coated Boyden chamber. In addition, we demonstrate the activation of above EMT markers, and the critical players involved in OPN-mediated cell signaling cascade using primary human hepatocytes infected with Japanese fulminant hepatitis (JFH)-1 HCV. Taken together, these studies suggest a potential role of OPN in inducing chronic liver disease and HCC associated with chronic HCV infection. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24498111/Role_of_hepatitis_C_virus_induced_osteopontin_in_epithelial_to_mesenchymal_transition_migration_and_invasion_of_hepatocytes_ L2 - http://dx.plos.org/10.1371/journal.pone.0087464 DB - PRIME DP - Unbound Medicine ER -