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Polo-like kinase-1 mediates hepatitis C virus-induced cell migration, a drug target for liver cancer.
El-Khobar, Korri E; Tay, Enoch; Diefenbach, Eve; Gloss, Brian S; George, Jacob; Douglas, Mark W.
Afiliação
  • El-Khobar KE; https://ror.org/04zj3ra44 Storr Liver Centre, Westmead Institute for Medical Researchhttps://ror.org/0384j8v12 , University of Sydney https://ror.org/04gp5yv64 at Westmead Hospital, Westmead, Australia.
  • Tay E; Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
  • Diefenbach E; https://ror.org/04zj3ra44 Storr Liver Centre, Westmead Institute for Medical Researchhttps://ror.org/0384j8v12 , University of Sydney https://ror.org/04gp5yv64 at Westmead Hospital, Westmead, Australia.
  • Gloss BS; https://ror.org/04zj3ra44 Protein Core Facility, Westmead Institute for Medical Research, Westmead, Australia.
  • George J; https://ror.org/04zj3ra44 Westmead Research Hub, Westmead Institute for Medical Research, Westmead, Australia.
  • Douglas MW; https://ror.org/04zj3ra44 Storr Liver Centre, Westmead Institute for Medical Researchhttps://ror.org/0384j8v12 , University of Sydney https://ror.org/04gp5yv64 at Westmead Hospital, Westmead, Australia.
Life Sci Alliance ; 6(11)2023 11.
Article em En | MEDLINE | ID: mdl-37648284
Polo-like kinase 1 (PLK1) is a regulator of cell mitosis and cytoskeletal dynamics. PLK1 overexpression in liver cancer is associated with tumour progression, metastasis, and vascular invasion. Hepatitis C virus (HCV) NS5A protein stimulates PLK1-mediated phosphorylation of host proteins, so we hypothesised that HCV-PLK1 interactions might be a mechanism for HCV-induced liver cancer. We used a HCV cell-culture model (Jc1) to investigate the effects of virus infection on the cytoskeleton. In HCV-infected cells, a novel posttranslational modification in ß-actin was observed with phosphorylation at Ser239. Using in silico and in vitro approaches, we identified PLK1 as the mediating kinase. In functional experiments with a phosphomimetic mutant form of ß-actin, Ser239 phosphorylation influences ß-actin polymerization and distribution, resulting in increased cell motility. The changes were prevented by treating cells with the PLK1 inhibitor volasertib. In HCV-infected hepatocytes, increased cell motility contributes to cancer cell migration, invasion, and metastasis. PLK1 is an important mediator of these effects and early treatment with PLK1 inhibitors may prevent or reduce HCC progression, particularly in people with HCV-induced HCC.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Hepatite C / Carcinoma Hepatocelular / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Life Sci Alliance Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Hepatite C / Carcinoma Hepatocelular / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Life Sci Alliance Ano de publicação: 2023 Tipo de documento: Article