2022 Fiscal Year Research-status Report
EPS8L3 mediates YAP nuclear translocation and promotes liver tumorigenesis
| Project/Area Number |
21K15401
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| Research Institution | Kagoshima University |
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Principal Investigator |
NGUYEN THAO 鹿児島大学, 医歯学域歯学系, 助教 (40733837)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | EPS8L3 / YAP / HCC / hepatocellular carcinoma / SH3 domain |
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| Outline of Annual Research Achievements |
EPS8L3 physically interacted with YAP, which induces the transcriptional activity of YAP through cytoplasmic sequestration and proteasomal degradation. EPS8L3 kinase activity was essential for protecting YAP from ubiquitin-mediated degradation and cytoplasmic retention. Downregulating EPS8L3 expression inhibited the survival of YAP-activated cancer cell lines and mouse xenograft models. EPS8L3 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human HCC. These results uncover EPS8L3 as a novel factor that regulates YAP stability and that targeting the YAP degradation pathway controlled by EPS8L3 is a potential strategy for suppressing YAP activity in cancer.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We completed in vitro and in vivo model and obtained significant results as we expected. Additionally, we extended our research model to other types of cancer. We reported our data in 81st annual meeting of Japanese Cancer Association and 112th annual meeting of the Japanese Society of Pathology and prepared the draft of our manscript.
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| Strategy for Future Research Activity |
We will try to complete all necessary experiements and data about the roles of EPS8L3 in hepatocellular carcinoma to have a publication. We are generating the specific peptide to prohibit the interaction between EPS8L3 and YAP, then examine its effects on malignant behaviors of HCC. Additionally, we will collaborate and continue our discovery about the interactions between EPS8L3 and YAP in oral cancer.
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| Causes of Carryover |
We planned to order the company to generate the specific peptide which is able to block the SH3 domain of EPS8L3 to prohibit the interaction between EPS8L3 and YAP. However, the discussion with company and peptide generation took more time than our expectation.
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