Ubiquitin-specific peptidase 14 maintains estrogen receptor α stability via its deubiquitination activity in endometrial cancer.
Ubiquitin-specific peptidase 14 maintains estrogen receptor α stability via its deubiquitination activity in endometrial cancer.
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泛素特异性肽酶 14 通过其去泛素化活性在子宫内膜癌中维持雌激素受体 α 的稳定性
DOI：
10.1016/j.jbc.2022.102734
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发表时间：
2023-01
影响因子：
4.8
通讯作者：
Zhao, Yue
中科院分区：
文献类型：
--
作者：
Su, Yingjie;Zeng, Kai;Liu, Shuchang;Wu, Yi;Wang, Chunyu;Wang, Shengli;Lin, Lin;Zou, Renlong;Sun, Ge;Luan, Ruina;Zhou, Baosheng;Bai, Yu;Niu, Jumin;Zhang, Yi;Zhao, Yue
子宫内膜癌（Endometrial cancer，EC）是妇科常见的恶性肿瘤之一，近年来发病率呈上升趋势。认为持续无对抗性雌激素暴露是EC发生的主要危险因素。因此，探讨雌激素/雌激素受体α（ERα）信号通路在EC中的调控作用，将有助于更好地理解EC的发生机制，并为EC的治疗寻找潜在的靶点。泛素特异性肽酶14（USP 14）是蛋白酶体相关去泛素化酶家族的成员，在一系列肿瘤中起着至关重要的作用。然而，USP 14在EC中的功能仍然是难以捉摸的。在此，我们的研究结果表明，与正常子宫内膜组织相比，USP 14在EC组织中高表达，并且USP 14的高表达与不良预后呈正相关。此外，USP 14通过其去泛素化活性维持ERα稳定性。我们的研究结果进一步表明，USP 14缺失降低了EC衍生细胞系中ERα调节基因的表达。此外，USP 14或USP 14特异性抑制剂处理的敲低显著抑制EC细胞系或小鼠中的细胞生长和迁移。我们进一步提供的证据表明，USP 14对EC细胞生长的影响，如果不是全部，至少部分与ERα通路有关。我们的研究为USP 14成为治疗EC的潜在治疗靶点提供了新的视角，特别是对于有生育保留需求的EC患者。
USP14 deubiquitinates ERα to maintain its stability in ECEndometrial cancer (EC) is one of the common gynecological malignancies of which the incidence has been rising for decades. It is considered that continuously unopposed estrogen exposure is the main risk factor for EC initiation. Thus, exploring the modulation of estrogen/estrogen receptor α (ERα) signaling pathway in EC would be helpful to well understand the mechanism of EC development and find the potential target for EC therapy. Ubiquitin-specific peptidase 14 (USP14), a member of the proteasome-associated deubiquitinating enzyme family, plays a crucial role in a series of tumors. However, the function of USP14 in EC is still elusive. Here, our results have demonstrated that USP14 is highly expressed in EC tissues compared with that in normal endometrial tissues, and higher expression of USP14 is positively correlated with poor prognosis. Moreover, USP14 maintains ERα stability through its deubiquitination activity. Our results further demonstrate that USP14 depletion decreases the expression of ERα-regulated genes in EC-derived cell lines. Moreover, knockdown of USP14 or USP14-specific inhibitor treatment significantly suppresses cell growth and migration in EC cell lines or in mice. We further provide the evidence to show that the effect of USP14 on EC cell growth, if not all, at least is partially related to ERα pathway. Our study provides new sights for USP14 to be a potential therapeutic target for the treatment of EC, especially for EC patients with fertility preservation needs.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.7
作者：
Backes FJ;Walker CJ;Goodfellow PJ;Hade EM;Agarwal G;Mutch D;Cohn DE;Suarez AA
通讯作者：
Suarez AA
影响因子：
16.6
作者：
Kravtsova-Ivantsiv, Yelena;Sommer, Thomas;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
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DOI：
10.1016/j.bbrc.2017.07.067
发表时间：
2017-09-09
影响因子：
3.1
作者：
Shi, Wei;Yan, Dan;Lin, Li
通讯作者：
Lin, Li
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin