RAC1b overexpression stimulates proliferation and NF-κB-mediated antiapoptotic signaling in thyroid cancer cells

Márcia Faria, Paula Matos, Teresa Pereira, Rafael Cabrera, Bruno A. Cardoso, Maria João Bugalho, Ana Luísa Silva

Resultado de pesquisarevisão de pares

19 Citações (Scopus)

Resumo

Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-κB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b- WT, confirming NF-κB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-κB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-κB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-κB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas.
Idioma originalEnglish
Número do artigoe0172689
Número de páginas13
RevistaPLoS ONE
Volume12
Número de emissão2
DOIs
Estado da publicaçãoPublished - 24 fev 2017
Publicado externamenteSim

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