RNA binding proteins modulate drug sensitivity of cancer chemotherapy via EMT related proteins.

• Project/Area Number: 25460921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: Kobayashi Takahiko 北海道大学, 医学(系)研究科(研究院), 研究員 (80333607)
• Co-Investigator(Kenkyū-buntansha): KOMATSU YOSHITO 北海道大学, 大学病院, 准教授 (60333598)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 薬剤耐性 / 抗癌剤耐性

Outline of Final Research Achievements

The biological basis of drug resistance against cancer chemotherapy has not been fully elucidated. RBM5 is known to modulate apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function remains to be examined. We show here that RBM5 modulates the expression of Snail, which is one of transcription factors that regulate epithelial-to-mesenchymal transition (EMT). EMT is a process whereby cells acquire morphologic and molecular alterations facilitating tumor metastasis and progression. Recent reports suggest that EMT contributes to the malignant potentials of cancer cells including the drug resistance. In the present study, we suggest that RBM5 plays important roles in the post-transcriptional regulation of mRNAs that are involved in the chemotherapeutic cellular responses.

Research Products

• [Journal Article] EGFR inhibitors prevent induction of cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition. (2015)
  • Author(s): Sato F, Kubota Y, Natsuizaka M, Maehara O, Hatanaka Y, Marukawa K, Terashita K, Suda G, Ohnishi S, Shimizu Y, Komatsu Y, Ohashi S, Kagawa S, Kinugasa H, Whelan KA, Nakagawa H, Sakamoto N.
  • Journal Title: Cancer Biol Ther Volume: 16 Issue: 6 Pages: 933940-933940
  • DOI: 10.1080/15384047.2015.1040959
  • Peer Reviewed
• [Journal Article] Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients (2015)
  • Author(s): Sasaki T, Fuse N, Kuwata T, Nomura S, Kaneko K, Doi T, Yoshino T, Asano H, Ochiai A, Komatsu Y, Sakamoto N, Ohtsu A
  • Journal Title: Jpn. J. Clin. Oncol Volume: 45 Issue: 1 Pages: 43-48
  • DOI: 10.1093/jjco/hyu174
  • Peer Reviewed
• [Journal Article] Large Solid-pseudopapillary Neoplasm of the Pancreas with Aberrant Protein Expression and Mutation of β-Catenin: A Case Report and Literature Review of the Distribution of β-Catenin Mutation (2013)
  • Author(s): Kobayashi T., Ozasa M., Miyashita K., Saga A., Miwa K., Saito M., Morioka M., Takeuchi M., Takenouchi N., Yabiku T., Kanno H., Yuzawa S., Tanino M., Tanaka S., Kawakami H., Asaka M., Sakamoto N.
  • Journal Title: Internal Medicine Volume: 52 Issue: 18 Pages: 2051-2056
  • DOI: 10.2169/internalmedicine.52.9512
  • NAID: 130003365837
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Knockdown of prothymosin α leads to apoptosis and developmental defects in zebrafish embryos. (2013)
  • Author(s): Emmanouilidou A., Karetsou Z., Tzima E., Kobayashi T., Papamarcaki T.
  • Journal Title: Biochem Cell Biol Volume: 91 Issue: 5 Pages: 325-332
  • DOI: 10.1139/bcb-2012-0103
  • Peer Reviewed