The mechanism of metastasis of esophageal cancer via Notch signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22846
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Osaka University
• Principal Investigator: Sugimoto Tomoki 大阪大学, 医学部附属病院, 医員 (20882244)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 食道癌 / EMT

Outline of Final Research Achievements

We found that EMT (Epithelial Mesenchymal Transition) was induced in the cells by 5-FU which is usually used in esophageal cancer treatment. At that time, cell morphology changed to a spindle shape, characteristic of mesenchymal cells, and the mesenchymal marker Vimentin was modulated. We also confirmed that Notch3 was inversely correlated with Vimentin. In addition, in animal experiments, we treated the mice implanted with subcutaneous tumors by 5-FU to make the cancer cells 5-FU resistant. The subcutaneous tumors showed an increase in Vimentin and a decrease in KRT14. From these results, we can see one of the mechanisms for the EMT transition.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

現在日本の最新の切除可能な食道癌の治療、切除不能進行食道癌の治療、いずれにおいても抗癌剤を用いることがガイドラインで定められており、特に5-FUは必ず用いることとなる。抗癌剤による効果は十分見込めるが、治療を続けている中で問題になるのが、癌細胞の獲得する抗癌剤耐性であり、今回の研究ではこの抗癌剤耐性のメカニズムのひとつであるEMTに着目した。今回の研究でEMTのメカニズムの一端を解明することができたことに加え、EMTは癌の転移を誘導することが知られており、今回見つけたメカニズムは癌細胞の転移とも関連づけられるかもしれない。