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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

28 Citazioni (Scopus)

Abstract

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 upregulation 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. ©2009 American Association for Cancer Research.
Lingua originaleEnglish
pagine (da-a)6141-6148
Numero di pagine8
RivistaCancer Research
Volume69
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Cancer Research
  • Oncology

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