河马信号通路
脱氮酶
邻近连接试验
癌症研究
磷酸化
泛素
免疫沉淀
癌症
生物
细胞生物学
信号转导
抑制器
细胞培养
受体
生物化学
遗传学
基因
作者
Dehai Wang,Zhongbo Li,Xin Li,CH Yan,Huijie Yang,Ting Zhuang,Xiao Wang,Yifeng Zang,Ziping Liu,Tianshi Wang,Rixia Jiang,Peng Su,Jian Zhu,Yinlu Ding
标识
DOI:10.1186/s13046-022-02410-5
摘要
Abstract Background The Hippo pathway functions as a tumor suppressor pathway in human cancers, while dysfunction of the Hippo pathway is frequently observed in malignancies. Although YAP/TAZ activity is tightly controlled by the phosphorylation cascade of the MST-LATS-YAP/TAZ axis, it is still unclear why the YAP/TAZ proteins are activated in human cancers despite Hippo pathway activation. Recent studies have suggested that in addition to phosphorylation, several other posttranslational modifications, including ubiquitination, also play critical roles in modulating TAZ function. Methods We used several gastric cancer cell lines and performed western blot analysis, real-time PCR, immunoprecipitation assays, and in vitro ubiquitination assays and established a xenograft mouse model. Results Here, by screening a DUB (deubiquitinase) siRNA library, we discovered that DUB1 functions as a critical modulator that facilitates gastric cancer stemness and progression by deubiquitinating and activating the TAZ protein. We also found that DUB1 expression was elevated in gastric cancer and that elevated DUB1 expression correlated with TAZ activation and poor survival. DUB1 associates with the TAZ protein and deubiquitinates TAZ at several lysine residues, which subsequently stabilizes TAZ and facilitates its function. Conclusions Our study revealed a novel deubiquitinase in the Hippo/TAZ axis and identified one possible therapeutic target for Hippo-driven gastric cancer.
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