The role of activin signaling in colorectal cancer EMT induction

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23882
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kanazawa University
• Principal Investigator: WANG DONG 金沢大学, ナノ生命科学研究所, 特任助教 (20842983)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: activin / driver gene mutation / colorectal cancer / EMT

Outline of Final Research Achievements

In order to know the role of activin in colorectal cancer EMT and which driver gene mutations contribute to activin's conversion from induction of apoptosis to induction of EMT, the organoids with different combination of driver gene mutations were simulated with activin and the cell survival and EMT were examined. Cell survival: by using activin simulation and blocking Kras-MEK signaling, we found that Kras mutation inhibits activin-induced apoptosis. Morphological changes: we found that activin induces EMT via interacting with p53 homozygous mutation. In vivo: activin pretreated organoids form more lung metastasis. For mechanism: by using RNA-seq, we found that under the regulation of activin and p53 homozygous mutation, some signaling pathways, such as Wnt, p38-MAPK, Stat3 signaling, were upregulated. According to these findings we will be able to test some inhibitors for inhibiting the morphological changes and the candidate inhibitors may be used for clinical trial.

Free Research Field

cancer biology

Academic Significance and Societal Importance of the Research Achievements

In this project, we explored the role and mechanism of activin in colorectal cancer EMT. We found that activin induces EMT by interacting with Kras and p53 mutations, which expands our knowledge about EMT mechanism and contributes to the development of anti-cancer drugs.