ERα Coregulator TRIM28 Promotes Breast Cancer Progression by Activating the AKT/GSK3β Pathway

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-08-07 DOI:10.1002/tox.24373
Linlin Fu, Baodong Ma, Lan Zhang, Huikang Xu, Wei Chen, Di Wu, Feng Gao, Yanping Huo
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Abstract

Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC.

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ERα核心调节因子TRIM28通过激活AKT/GSK3β通路促进乳腺癌进展
雌激素受体α(ERα)能促进ER阳性乳腺癌(BC)细胞的生长和存活。在雌激素的激活下,ER通过直接与特定的雌激素反应元件结合来调节ER表达的靶基因。本研究采用 RIME 方法鉴定了 BC 细胞系 MCF7 中与内源性染色质结合的 ER 相互作用的 106 个蛋白。相互作用组数据显示,含三方基序 28(TRIM28)是ER相关蛋白中富集最显著的蛋白。这项研究提供的证据表明,TRIM28的表达提高了ER转录活性,促进了BC细胞的增殖、迁移和侵袭。TRIM28的高表达与ER阳性BC患者的不良临床预后有关。机理实验表明,TRIM28的表达激活了AKT/GSK3β通路。总之,TRIM28是ER和AKT信号转导的调控蛋白,因此可以作为治疗BC的靶点。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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