Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy

Matilde Todaro, Giorgio Stassi, Gaspare Gulotta, Giuseppe Buscemi, Francesco Dieli, Miriam Bini, Maria Giovanna Francipane, Vincenzo Eterno, Valentina Spina, Giorgio Stassi, Matilde Todaro, Ruggero De Maria, Maria Giovanna Francipane, Valentina Spina, Vincenzo Eterno

Risultato della ricerca: Articlepeer review

30 Citazioni (Scopus)


We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the highly aggressive anaplastic thyroid cancer cells reduces or abolishes STAT3 and 6 phosphorylation and PI3K/Akt pathway activation resulting in alteration in the balance of proapoptotic and antiapoptotic molecules and sensitization to chemotherapeutic drugs in vitro. Likewise, exogenous expression of SOCS3 significantly reduces tumor growth and potently enhances the efficacy of chemotherapy in vivo. Our results indicate that SOCS3 regulation of cytokines-prosurvival programs might represent a new strategy to overcome the resistance to chemotherapy-induced cell death of thyroid cancer.
Lingua originaleEnglish
pagine (da-a)6141-6148
Numero di pagine8
RivistaCancer Research
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1306???


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