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RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive manner.
Luis-Ravelo, Diego; Antón, Iker; Zandueta, Carolina; Valencia, Karmele; Pajares, María-José; Agorreta, Jackeline; Montuenga, Luis; Vicent, Silvestre; Wistuba, Ignacio I; De Las Rivas, Javier; Lecanda, Fernando.
Afiliação
  • Luis-Ravelo D; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Antón I; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Zandueta C; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Valencia K; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Pajares MJ; Biomarkers Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Agorreta J; Biomarkers Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Montuenga L; Biomarkers Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Vicent S; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • Wistuba II; Department of Pathology, The University of Texas - M. D. Anderson Cancer Center, Houston, TX, USA.
  • De Las Rivas J; Bioinformatics and Functional Genomics Research Group, Cancer Research Center, University of Salamanca (CSIC/USAL), Salamanca, Spain.
  • Lecanda F; Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. Electronic address: flecanda@unav.es.
Mol Oncol ; 8(2): 196-206, 2014 Mar.
Article em En | MEDLINE | ID: mdl-24321314
Lung adenocarcinoma (ADC) is the most common lung cancer subtype and presents a high mortality rate. Clinical recurrence is often associated with the emergence of metastasis and treatment resistance. The purpose of this study was to identify genes with high prometastatic activity which could potentially account for treatment resistance. Global transcriptomic profiling was performed by robust microarray analysis in highly metastatic subpopulations. Extensive in vitro and in vivo functional studies were achieved by overexpression and by silencing gene expression. We identified the small GTPase RHOB as a gene that promotes early and late stages of metastasis in ADC. Gene silencing of RHOB prevented metastatic activity in a systemic murine model of bone metastasis. These effects were highly dependent on tumor-host interactions. Clinical analysis revealed a marked association between high RHOB levels and poor survival. Consistently, high RHOB levels promote metastasis progression, taxane-chemoresistance, and contribute to the survival advantage to γ-irradiation. We postulate that RHOB belongs to a novel class of "genes of recurrence" that have a dual role in metastasis and treatment resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Adenocarcinoma / Resistencia a Medicamentos Antineoplásicos / Proteína rhoB de Ligação ao GTP / Neoplasias Pulmonares / Proteínas de Neoplasias Tipo de estudo: Diagnostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ósseas / Adenocarcinoma / Resistencia a Medicamentos Antineoplásicos / Proteína rhoB de Ligação ao GTP / Neoplasias Pulmonares / Proteínas de Neoplasias Tipo de estudo: Diagnostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article