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.
乳腺癌是女性中最常被诊断出的恶性肿瘤，也是癌症相关死亡的主要原因之一。大多数乳腺肿瘤具有激素依赖性，其中雌激素信号通路在促进这些细胞的存活及恶性行为中起着关键作用。雌激素信号通路涉及配体激活的胞质雌激素受体，该受体与多种共调节因子（如类固醇受体共激活因子家族成员）共同转位至细胞核，结合靶基因启动子并调控其表达。SRC-3作为该家族成员，能够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，但研究显示其在乳腺癌中存在扩增和过表达现象，并能促进恶性肿瘤进展。SRC-3促癌潜能的多样性体现在既促进肿瘤细胞的恶性行为，又塑造具有免疫抑制表型的肿瘤微环境。它还能抑制具有效应功能的肿瘤浸润淋巴细胞募集，并促进肿瘤干细胞特性。此外，SRC-3还参与乳腺癌治疗过程中对激素疗法和免疫疗法耐药性的形成。SRC-3通过这种多途径促进乳腺癌恶性的特性，使其成为理想的治疗靶点，系统性靶向SRC-3可能对乳腺癌治疗的成功具有重要意义。
肿瘤(癌症)患者之家