揭示肝细胞癌的侵袭：STAMBPL1 介导的 TRAF2 去泛素化激活了 WNT/PI3K/NF-kb 信号通路。

IF 5.7 2区生物学 Q1 BIOLOGY

Biology Direct Pub Date : 2024-02-28 DOI:10.1186/s13062-024-00460-7

Zhihuai Wang, Yinjie Zhang, Yuhang Shen, Haiyang Zhou, Yuan Gao, Chunfu Zhu, Xihu Qin

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引用次数: 0

摘要

STAM Binding Protein Like 1（STAMBPL1）是一种去泛素化酶（DUB），在各类癌症中发挥着重要作用。然而，它作为 DUB 参与 HCC 肿瘤发生和进展的作用仍不清楚。该研究发现，STAMBPL1 在 HCC 患者中上调并具有很高的预后价值。在功能上，STAMBPL1能显著促进HCC细胞的增殖和转移，并与TRAF2相互作用，通过K63残基的去泛素化使其稳定。STAMBPL1 过表达后，TRAF2 上调，P65 蛋白进入细胞核，激活了 WNT/PI3K/ NF-kb 信号通路。STAMBPL1的251-436位点尤其与TRAF2的294-496位点相互作用，从而发挥DUB的功能，清除附着在TRAF2上的泛素分子。我们的研究揭示了STAMBPL1在介导TRAF2去泛素化和稳定化方面的新功能，从而激活了WNT/PI3K/NF-kb信号通路，提示其有可能成为HCC的新型生物标志物和治疗靶点。

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Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.

STAM Binding Protein Like 1 (STAMBPL1), functions as a deubiquitinase (DUB) and plays a significant role in various types of cancers. However, its effect as a DUB participating in the HCC tumorigenesis and progression still unknown. In the study, the upregulation and strong prognosis value of STAMBPL1 were identified in HCC patients. Functionally, STAMBPL1 significantly promoted HCC cells proliferation and metastasis, and it interacts with TRAF2 and stabilize it via the deubiquitination at the K63 residue. The TRAF2 upregulation stabilized by STAMBPL1 overexpression transfers of P65 protein into the nucleus and activates the WNT/PI3K/ NF-kb signaling pathway. The 251-436 sites of STAMBPL1 particularly interact with the 294-496 sites of TRAF2, thereby exerting the function of DUB and removing the ubiquitin molecules attached to TRAF2. Our research unveiled a new function of STAMBPL1 in mediating TRAF2 deubiquitination and stabilization, thereby activating the WNT/PI3K/NF-kb signaling pathway, suggesting its potential as a novel biomarker and therapeutic target for HCC.

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来源期刊

Biology Direct 生物-生物学

CiteScore

6.40

自引率

10.90%

发文量

审稿时长

7 months

期刊介绍： Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.