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SRC-3 在乳腺癌发生和发展中的关键作用,使其成为有前景的临床靶点

英文原题:Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.

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Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.

PubMed 2023/10/31(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

乳腺癌(BCa)是女性中最常被诊断的恶性肿瘤,也是癌症相关死亡的主要原因之一。大多数乳腺肿瘤是激素依赖性的,雌激素信号在促进这些细胞的生存和恶性行为中起着关键作用。雌激素信号涉及配体激活的细胞质雌激素受体,这些受体与各种共调节因子(如类固醇受体共激活因子(SRC)家族成员)一起转位至细胞核,并结合到靶基因的启动子上,调节其表达。SRC-3是该家族的一员,它与配体激活的雌激素受体相互作用并增强其转录活性。尽管SRC-3在正常稳态和发育过程中具有重要作用,但已被证明在乳腺癌中扩增和过表达,并促进恶性程度。SRC-3促进恶性的潜力是多样的,既涉及促进肿瘤细胞的恶性行为,也涉及创建具有免疫抑制表型的肿瘤微环境。SRC-3还抑制具有效应功能的TIL(肿瘤浸润淋巴细胞)的募集,并促进干性。

此外,SRC-3还参与乳腺癌治疗过程中对激素治疗和免疫治疗耐药性的发展。SRC-3以这种方式促进乳腺癌恶性的多功能性使其成为一个良好的靶点,系统地靶向SRC-3可能对乳腺癌治疗的成功具有重要意义。

展开英文摘要原文

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators, such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression.

SRC-3 is a member of this family that interacts with, and enhances, the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy.

The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness.

Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

论文信息

作者
Varisli L、Dancik GM、Tolan V、Vlahopoulos S
第一作者单位
Department of Molecular Biology and Genetics, Science Faculty, Dicle University, Diyarbakir 21280, Turkey.Turkey
通讯作者单位
First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, Goudi, 11527 Athens, Greece.Greece
文献类型
综述
期刊
Cancers2023 Oct 31
原文标识
PubMed 37958417 · DOI 10.3390/cancers15215242