Functional analysis and expression of YB-1 in cancer cells, for integrated understanding

• Project/Area Number: 24501323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: KOHNO Kimitoshi 産業医科大学, 名誉教授, 名誉教授 (00153479)
• Co-Investigator(Kenkyū-buntansha): SASAGURI Yasuyuki 産業医科大学, 医学部, 教授 (60140646) ; WANG Ke-Yong 産業医科大学, 共同利用研究センター, 准教授 (30369053)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 抗がん剤 / がん化学療法 / 耐性 / 転写関連因子 / 薬剤感受性 / Y-box binding protein 1 / Topoisomerase 1 / Drug resistance / がん制御遺伝子

Outline of Final Research Achievements

In this study, our findings suggest that YB-1 located in the nucleus serves as an intracellular promoter of TOPO1 catalytic activity through direct interaction with TOPO1, but meanwhile, it also enhances the sensitivity of TOPO1 inhibitor camptothecin (CPT). In addition, we examined the expression of YB-1in various solid tumors. In gastric cancer, the level of YB-1 expression significantly differed with respect to various histopathological classification. Nevertheless, YB-1 promotes cancer progression in both cancer cells and vascular endothelial cells, thus it is suggested to be a potential biomarker for gastric cancer.　As an integrated achievement of the past studies related to this research theme, it has became a registered patent, “a new biomarker of tumor neovessels and its endothelial cells, and a cancer therapeutic drug that use it as the target.” (Patent number: 5697010) in February, 2015.

Research Products

• [Journal Article] Y-box binding protein 1 expression in gastric cancer subtypes and association with cancer neovasculature (2015)
  • Author(s): Wu Y, Wang KY, Li Z, Liu YP, Izumi H, Uramoto H, Nakayama Y, Ito KI, Kohno K.
  • Journal Title: Clinical and Translational Oncology Volume: 17 Issue: 2 Pages: 152-159
  • DOI: 10.1007/s12094-014-1208-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Y-box binding protein 1 enhances DNA topoisomerase 1 activity and sensitivity to camptothecin via direct interaction. (2014)
  • Author(s): Wu Y, Wang KY, Li Z, Liu YP, Izumi H, Uramoto H, Nakayama Y, Ito KI, Kohno K.
  • Journal Title: Journal of Experimental & Clinical Cancer Research Volume: 33 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s13046-014-0112-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peroxiredoxins, thioredoxin, and Y-box-binding protein-1 are involved in the pathogenesis and progression of dialysis-associated renal cell carcinoma (2013)
  • Author(s): Fushimi F., Taguchi K., Izumi H., Kohno K., Kuwano M., Ono M., Nakashima Y., Takesue T., Naito S., Oda Y.
  • Journal Title: Virchows Archiv Volume: 463 Issue: 4 Pages: 553-562
  • DOI: 10.1007/s00428-013-1460-y
  • Peer Reviewed
• [Journal Article] Strong YB-1 expression is associated with liver metastasis progression and predicts shorter disease-free survival in advanced gastric cancer. (2012)
  • Author(s): Wu, Y., Yamada, S., Izumi, H., Li, Z., Shimajiri, S., Wang, K.Y., Liu, Y.P., Kohno, K., Sasaguri, Y.
  • Journal Title: Journal of Surgical Oncology Volume: 105 Issue: 7 Pages: 724-730
  • DOI: 10.1002/jso.23030
  • Peer Reviewed
• [Journal Article] Alteration of Y-box binding protein-1 expression modifies the response to endocrine therapy in estrogen receptor-positive breast cancer. (2012)
  • Author(s): Ito, T., Kamijo, S., Izumi, H., Kohno, K., Amano, J., Ito, K.
  • Journal Title: Breast Cancer Research and Treatment Volume: 133 Issue: 1 Pages: 145-159
  • DOI: 10.1007/s10549-011-1731-8
  • Peer Reviewed
• [Journal Article] Association of Nuclear YB-1 Localization With Lung Resistance-related Protein and Epidermal Growth Factor Receptor Expression in Lung Cancer. (2012)
  • Author(s): Hyogotani, A., Ito, K., Yoshida, K., Izumi, H., Kohno, K., Amano, J.
  • Journal Title: Clinical Lung Cancer Volume: 13 Issue: 5 Pages: 375-384
  • DOI: 10.1016/j.cllc.2011.11.006
  • Peer Reviewed
• [Presentation] Y-box binding protein 1 expression in gastric cancer (2015)
  • Author(s): 王 克よん
  • Organizer: 日本病理学会総会
  • Place of Presentation: 愛知県名古屋市 名古屋国際会議場
  • Year and Date: 2015-04-30 – 2015-05-02