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 journalArticle

10 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 1 2013

Fingerprint

Kidney Neoplasms
Transducers
Interferons
Proteolysis
Renal Cell Carcinoma
Y-Box-Binding Protein 1
T-Lymphocytes
Therapeutic Uses
Immunotherapy
Neoplasms
Therapeutics
Down-Regulation
Lymphocytes
Kidney
Drug Therapy
Survival

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α. / Takeuchi, Ario; Shiota, Masaki; Tatsugami, Katsunori; Yokomizo, Akira; Kuroiwa, Kentaro; Dejima, Takashi; Tanaka, Shingo; Itsumi, Momoe; Eto, Masatoshi; Naito, Seiji.

In: Cancer Immunology, Immunotherapy, Vol. 62, No. 3, 01.03.2013, p. 517-527.

Research output: Contribution to journalArticle

Takeuchi, Ario ; Shiota, Masaki ; Tatsugami, Katsunori ; Yokomizo, Akira ; Kuroiwa, Kentaro ; Dejima, Takashi ; Tanaka, Shingo ; Itsumi, Momoe ; Eto, Masatoshi ; Naito, Seiji. / YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α. In: Cancer Immunology, Immunotherapy. 2013 ; Vol. 62, No. 3. pp. 517-527.
@article{b18e91c1f6cd4d94bb52f9cc5d366197,
title = "YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α",
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.",
author = "Ario Takeuchi and Masaki Shiota and Katsunori Tatsugami and Akira Yokomizo and Kentaro Kuroiwa and Takashi Dejima and Shingo Tanaka and Momoe Itsumi and Masatoshi Eto and Seiji Naito",
year = "2013",
month = "3",
day = "1",
doi = "10.1007/s00262-012-1356-8",
language = "English",
volume = "62",
pages = "517--527",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "3",

}

TY - JOUR

T1 - YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α

AU - Takeuchi, Ario

AU - Shiota, Masaki

AU - Tatsugami, Katsunori

AU - Yokomizo, Akira

AU - Kuroiwa, Kentaro

AU - Dejima, Takashi

AU - Tanaka, Shingo

AU - Itsumi, Momoe

AU - Eto, Masatoshi

AU - Naito, Seiji

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84877134575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877134575&partnerID=8YFLogxK

U2 - 10.1007/s00262-012-1356-8

DO - 10.1007/s00262-012-1356-8

M3 - Article

C2 - 23052245

AN - SCOPUS:84877134575

VL - 62

SP - 517

EP - 527

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 3

ER -