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Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects.
Espinha, Gisele; Osaki, Juliana Harumi; Costa, Erico Tosoni; Forti, Fabio Luis.
Afiliação
  • Espinha G; Laboratory of Signaling in Biomolecular Systems, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
  • Osaki JH; Laboratory of Signaling in Biomolecular Systems, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
  • Costa ET; Centro de Oncologia Molecular, Hospital Sirio Libanes, 01308-060 Sao Paulo, SP, Brazil; Ludwig Institute for Cancer Research (LICR), 01509-010 Sao Paulo, SP, Brazil.
  • Forti FL; Laboratory of Signaling in Biomolecular Systems, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
Oxid Med Cell Longev ; 2016: 2696952, 2016.
Article em En | MEDLINE | ID: mdl-26823948
Ultraviolet radiation is the main cause of DNA damage to melanocytes and development of melanoma, one of the most lethal human cancers, which leads to metastasis due to uncontrolled cell proliferation and migration. These phenotypes are mediated by RhoA, a GTPase overexpressed or overactivated in highly aggressive metastatic tumors that plays regulatory roles in cell cycle progression and cytoskeleton remodeling. This work explores whether the effects of UV on DNA damage, motility, proliferation, and survival of human metastatic melanoma cells are mediated by the RhoA pathway. Mutant cells expressing dominant-negative (MeWo-RhoA-N19) or constitutively active RhoA (MeWo-RhoA-V14) were generated and subjected to UV radiation. A slight reduction in migration and invasion was observed in MeWo and MeWo-RhoA-V14 cells but not in MeWo-RhoA-N19 cells, which presented inefficient motility and invasiveness associated with stress fibers fragmentation. Proliferation and survival of RhoA-deficient cells were drastically reduced by UV compared to cells displaying normal or high RhoA activity, suggesting increased sensitivity to UV. Loss of RhoA activity also caused less efficient DNA repair, with elevated levels of DNA lesions such as strand breaks and cyclobutane pyrimidine dimers (CPDs). Thus, RhoA mediates genomic stability and represents a potential target for sensitizing metastatic tumors to genotoxic agents.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Raios Ultravioleta / Proteína rhoA de Ligação ao GTP / Melanoma Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Raios Ultravioleta / Proteína rhoA de Ligação ao GTP / Melanoma Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos