癌症研究
胰腺癌
癌变
导管细胞
胰腺导管腺癌
医学
癌症
生物
胰腺
内科学
作者
Tiantian Jing,Xiaoli Xu,Chengsi Wu,Tiantian Jing,Lili Yuan,Yiwen Huang,Yizhen Liu,Boshi Wang
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-11-01
卷期号:577: 216444-216444
被引量:1
标识
DOI:10.1016/j.canlet.2023.216444
摘要
Pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), a necessary process for pancreatic ductal adenocarcinoma (PDAC) initiation. However, the regulatory role of POH1, a deubiquitinase linked to several types of cancer, in ADM and PDAC is unclear. In this study, we investigated the role of POH1 in ADM and PDAC using murine models. Our findings suggest that pancreatic-specific deletion of Poh1 alleles attenuates ADM and impairs pancreatic carcinogenesis, improving murine survival. Mechanistically, POH1 deubiquitinates and stabilizes the MYC protein, which potentiates ADM and PDAC. Furthermore, POH1 is highly expressed in PDAC samples, and clinical evidence establishes a positive correlation between aberrantly expressed POH1 and poor prognosis in PDAC patients. Targeting POH1 with a specific small-molecule inhibitor significantly reduces pancreatic tumor formation, highlighting POH1 as a promising therapeutic target for PDAC treatment. Overall, POH1-mediated MYC deubiquitination is crucial for ADM and PDAC onset, and targeting POH1 could be an effective strategy for PDAC treatment, offering new avenues for PDAC targeted therapy.
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