American Association for Cancer Research
00085472can082976-sup-stab_1.pdf (96.84 kB)

Supplementary Table 1 from ADAM23 Negatively Modulates αvβ3 Integrin Activation during Metastasis

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posted on 2023-03-30, 18:52 authored by Newton V. Verbisck, Érico T. Costa, Fabrício F. Costa, Felícia P. Cavalher, Michele D.M. Costa, Angelita Muras, Valéria A. Paixão, Ricardo Moura, Mariana F. Granato, Daniela F Ierardi, Tamara Machado, Fabiana Melo, Karina B. Ribeiro, Isabela W. Cunha, Vladmir C.C. Lima, Maria do Socorro Maciel, André L. Carvalho, Fernando F. Soares, Silvio Zanata, Mari C. Sogayar, Roger Chammas, Anamaria A. Camargo
Supplementary Table 1 from ADAM23 Negatively Modulates αvβ3 Integrin Activation during Metastasis



The ADAM23 gene is frequently silenced in different types of tumors, and, in breast tumors, silencing is correlated with tumor progression, suggesting that it might be associated with the acquisition of a metastatic phenotype. ADAM23 exerts its function mainly through the disintegrin domain, because its metalloprotease domain is inactive. Analysis of ADAM23 binding to integrins has revealed a specific interaction with αvβ3 integrin mediated by the disintegrin domain. Altered expression of αvβ3 integrin has been observed in different types of tumors, and expression of this integrin in the activated form has been shown to promote metastasis formation. Here, we investigated the possibility that interaction between ADAM23 and αvβ3 integrin might negatively modulate αvβ3 activation during metastatic progression. ADAM23 expression was knocked down using short hairpin RNA in the MDA-MB-435 cell line, which has been extensively used as a model for αvβ3 integrin activation. Ablation of ADAM23 enhanced αvβ3 integrin activation by at least 2- to 4-fold and ADAM23 knockdown cells showed enhanced migration and adhesion to classic αvβ3 integrin ligands. Ablation of ADAM23 expression also enhanced pulmonary tumor cell arrest in immunodeficient mice. To complement our findings with clinical evidence, we showed that silencing of ADAM23 gene by DNA promoter hypermethylation in a collection of 94 primary breast tumors was significantly associated with lower distant metastases–free and disease-specific survivals and was an independent prognostic factor for poor disease outcome. Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating αvβ3 integrin activation. [Cancer Res 2009;69(13):5546–52]

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