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

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

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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.

Original languageEnglish
Pages (from-to)6141-6148
Number of pages8
JournalCancer Research
Volume69
Issue number15
DOIs
Publication statusPublished - Aug 1 2009

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Francipane, M. G., Eterno, V., Spina, V., Bini, M., Scerrino, G., Buscemi, G., Gulotta, G., Todaro, M., Dieli, F., De Maria, R., & Stassi, G. (2009). Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy. Cancer Research, 69(15), 6141-6148. https://doi.org/10.1158/0008-5472.CAN-09-0994