基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.
Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.
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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。
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.
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