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Inhibition of adhesion, migration and of α5ß1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A.
Pelillo, Chiara; Mollica, Hilaria; Eble, Johannes A; Grosche, Julius; Herzog, Lea; Codan, Barbara; Sava, Gianni; Bergamo, Alberta.
Afiliación
  • Pelillo C; Callerio Foundation Onlus, Trieste, Italy.
  • Mollica H; Callerio Foundation Onlus, Trieste, Italy.
  • Eble JA; Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany.
  • Grosche J; Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany.
  • Herzog L; Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany.
  • Codan B; Dept of Engineering and Architecture, University of Trieste, Italy.
  • Sava G; Callerio Foundation Onlus, Trieste, Italy; Dept of Life Sciences, University of Trieste, Italy.
  • Bergamo A; Callerio Foundation Onlus, Trieste, Italy.
J Inorg Biochem ; 160: 225-35, 2016 07.
Article en En | MEDLINE | ID: mdl-26961176
NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium-based drug characterised by the selective activity against tumour metastases. Previously we have shown the influence of the hepatic microenvironment to direct the arrest of the metastatic cells of colorectal cancer. Here we used the experimental model of HCT-116 colorectal cancer cells in vitro to explore whether the interference with α5ß1 integrin may mechanistically explain the anti-metastatic effect of NAMI-A. NAMI-A inhibits two important steps of the tumour metastatic progression of colorectal cancer, i.e. the adhesion and migration of the tumour cells on the extracellular matrix proteins. The fibronectin receptor α5ß1 integrin is likely involved in the anti-adhesive effects of NAMI-A on the HCT-116 colorectal cancer cells during their interaction with the extracellular matrix. Mechanistically, NAMI-A decreases the α5ß1 integrin expression, and reduces FAK (Focal Adhesion Kinase) auto-phosphorylation on Tyr397, an important signalling event, involved in α5ß1 integrin activation. These effects were validated by siRNA-induced knock down of the α5 integrin subunit and/or by the use of specific blocking mAbs against the active site of the integrin. Our results demonstrate the relevance of α5ß1 integrin for colorectal cancer. We also show that the anti-metastatic effect of NAMI-A depends on the modulation of this integrin. Thus, our data on NAMI-A support the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organometálicos / Rutenio / Regulación Neoplásica de la Expresión Génica / Dimetilsulfóxido / Integrina alfa5beta1 / Quinasa 1 de Adhesión Focal / Antineoplásicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organometálicos / Rutenio / Regulación Neoplásica de la Expresión Génica / Dimetilsulfóxido / Integrina alfa5beta1 / Quinasa 1 de Adhesión Focal / Antineoplásicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos