YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α

Ario Takeuchi, Masaki Shiota, Katsunori Tatsugami, Akira Yokomizo, Kentaro Kuroiwa, Takashi Dejima, Shingo Tanaka, Momoe Itsumi, Masatoshi Eto, Seiji Naito

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Renal cell carcinoma (RCC) accounts for 80-95 % of kidney tumors, and approximately 30 % of RCC patients have metastatic disease at diagnosis. Conventional chemotherapy is not effective in patients with metastatic RCC (MRCC); therefore, immunotherapy with interferon-α (IFN-α) has been employed to improve survival. However, the response rate of MRCC to IFN-α therapy is low. We previously reported that a signal transducer and activator 3 (STAT3) polymorphism was a useful diagnostic marker to predict the response to IFN-α therapy in patients with MRCC. Therefore, we hypothesized the inhibition of STAT3 in the addition of IFN-α therapy might be useful. Moreover, the blockage of STAT3 itself has been reported to enhance the antitumor effects. However, because IFN-α is thought to elicit its therapeutic effect via enhancement of an antitumor immune response mediated by lymphocytes that can be activated by IFN-α administrations, it is probable that the suppression of STAT3 in vivo relates to autoimmune disorders. In the present study, we found Y-box binding protein-1 (YB-1) was poorly expressed in T lymphocytes, as compared with cancer tissues. YB-1 was reported to have an important effect on the STAT3 pathway. Suppression of STAT3 by YB-1 inhibition did not seem to enhance the potential risk for autoimmune disorders. Moreover, we found sensitivity to IFN-α was increased by YB-1 suppression, and this suppression did not down-regulate IFN-α activation of T lymphocytes.

Original languageEnglish
Pages (from-to)517-527
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume62
Issue number3
DOIs
Publication statusPublished - Mar 2013

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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