Molecular link between stress response and cancer and its clinical implication

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09396
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kindai University
• Principal Investigator: SAKURAI Toshiharu 近畿大学, 医学部, 講師 (90397539)
• Co-Investigator(Kenkyū-buntansha): 工藤 正俊 近畿大学, 医学部, 教授 (10298953)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 炎症性腸疾患

Outline of Final Research Achievements

Stress responses to chronic inflammation promote the development of colorectal and liver cancer. Using knock-out mice, we clarified the role of Heat shock protein (HSP) 27 for tumorigenesis in the liver and colon. HSP27 is involved in the pathogenesis of liver and colorectal cancer. Gankyrin (GK) is an oncoprotein which regulates inflammatory responses and its inhibition is considered as a possible anti-inflammatory therapy for inflammatory bowel disease (IBD). Unexpectedly, GK-deficiency in the upper small bowel augmented inflammatory activity. Examination of human samples have confirmed that the reduction of GK expression in the small bowel is associated with colonic involvement in human Crohn’s disease. Through the sequencing of bacterial 16S rRNA gene amplicons, bacteria potentially deleterious to intestinal homeostasis were identified. These results provide important insights into the pathogenesis of IBD.

Free Research Field

炎症性腸疾患と消化器癌

Academic Significance and Societal Importance of the Research Achievements

大腸上皮細胞および肝実質細胞でのHSP27の機能を解明し、新しい治療およびバイオマーカーの標的分子としての有用性が明らかとなった。大腸粘膜におけるHSP27の発現量は発癌リスクの予測に有用である。またWhole transcriptome解析により、炎症性腸疾患関連大腸癌の再発と相関する遺伝子セットを同定した。本研究の成果は大腸癌サーベイランスの効率化につながる。次世代シークエンサーを用いた解析により、TNF阻害薬の治療効果を予測する遺伝子セットおよび腸内細菌叢を同定した。炎症性疾患および癌領域における個別医療の実現に向けて、更なるデータの蓄積を行っていく。