EPS8L3 mediates YAP nuclear translocation and promotes liver tumorigenesis

EPS8L3介导YAP核易位并促进肝脏肿瘤发生

• 批准号: 21K15401
• 负责人: NGUYEN THAO
• 金额: $ 3万
• 依托单位: Kagoshima University (2022)Hiroshima University (2021)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15401/
• 关键词: EPS8L3; YAP; HCC; hepatocellular carcinoma; SH3 domain; Hepatocellularcarcinoma; Liver cancer; Carcinogenesis

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.

EPS8L3与雅普物理相互作用，其通过胞质螯合和蛋白酶体降解诱导雅普的转录活性。EPS8L3激酶活性对于保护雅普免受泛素介导的降解和细胞质滞留是必不可少的。下调EPS8L3表达抑制了YAP激活的癌细胞系和小鼠异种移植模型的存活。EPS8L3上调与临床肿瘤样品中高水平的雅普表达和不良预后相关，证实了其在人HCC中雅普活性的重要作用。这些结果揭示了EPS8L3作为调节雅普稳定性的新因子，并且靶向由EPS8L3控制的雅普降解途径是抑制癌症中雅普活性的潜在策略。

项目成果

EPS8L3 mediates YAP nuclear translocation and promotes liver tumorigenesis

EPS8L3介导YAP核易位并促进肝脏肿瘤发生

• 发表时间: 2023
• 作者: Phuong Thao Nguyen;Kaori Shima;Yudai Shimojukkoku;Tomonori Sasahira
• 通讯作者: Tomonori Sasahira

Analysis of METTL5 expression and function in oral squamous cell carcinoma

METTL5在口腔鳞癌中的表达及功能分析

• 发表时间: 2023
• 作者: Kaori Shima;Phuong Thao Nguyen;Yudai Shimojukkoku;Tomonori Sasahira
• 通讯作者: Tomonori Sasahira

Impacts of KPNA7 amplification and overexpression on tumor infiltrating immune cells of HNSCCs

KPNA7扩增和过表达对HNSCC肿瘤浸润免疫细胞的影响

• 发表时间: 2023
• 作者: Phuong Thao Nguyen;Kaori Shima;Yudai Shimojukkoku;Tomonori Sasahira
• 通讯作者: Tomonori Sasahira

The roles of MCTP2 in oral squamous cell carcinoma

MCTP2在口腔鳞状细胞癌中的作用

• 发表时间: 2023
• 作者: Ayami Tomishima，Phuong Thao Nguyen;Kaori Shima;Yudai Shimojukkoku;Tomonori Sasahira.
• 通讯作者: Tomonori Sasahira.

Cytoplasmic TCF19 translocation impairs DNA damage repair in HNSCC

细胞质 TCF19 易位损害 HNSCC 中的 DNA 损伤修复

• 发表时间: 2023
• 作者: Yasunobu Oku;Phuong Thao Nguyen;Kaori Shima;Yudai Shimojukkoku;Tomonori Sasahira
• 通讯作者: Tomonori Sasahira