癌症研究
基因敲除
热休克蛋白90
细胞生长
车站3
癌变
化学
信号转导
热休克蛋白
细胞生物学
医学
内科学
生物
生物化学
癌症
细胞凋亡
基因
作者
Liting Zhou,Ning Yao,Lu Yang,Kangdong Liu,Yan Qiao,Chuntian Huang,Ruijuan Du,Yiu To Yeung,Wenting Liu,Daizhan Cheng,Zigang Dong,Xiang Li
出处
期刊:Cell Reports
[Elsevier]
日期:2023-05-01
卷期号:42 (5): 112445-112445
被引量:2
标识
DOI:10.1016/j.celrep.2023.112445
摘要
The molecular and pathogenic mechanisms of esophageal squamous cell carcinoma (ESCC) development are still unclear, which hinders the development of effective treatments. In this study, we report that DUSP4 is highly expressed in human ESCC and is negatively correlated with patient prognosis. Knockdown of DUSP4 suppresses cell proliferation and patient-derived xenograft (PDX)-derived organoid (PDXO) growth and inhibits cell-derived xenograft (CDX) development. Mechanistically, DUSP4 directly binds to heat shock protein isoform β (HSP90β) and promotes the ATPase activity of HSP90β by dephosphorylating HSP90β on T214 and Y216. These dephosphorylation sites are critical for the stability of JAK1/2-STAT3 signaling and p-STAT3 (Y705) nucleus translocation. In vivo, Dusp4 knockout in mice significantly inhibits 4-nitrochinoline-oxide-induced esophageal tumorigenesis. Moreover, DUSP4 lentivirus or treatment with HSP90β inhibitor (NVP-BEP800) significantly impedes PDX tumor growth and inactivates the JAK1/2-STAT3 signaling pathway. These data provide insight into the role of the DUSP4-HSP90β-JAK1/2-STAT3 axis in ESCC progression and describe a strategy for ESCC treatment.
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