Department of Breast Surgery, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, PR China.
Department of Pathology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, PR China.
SLAS Technol. 2024 Oct;29(5):100190. doi: 10.1016/j.slast.2024.100190. Epub 2024 Sep 17.
Abnormal expression of connexin 43 (Cx43) contributes to the development and progression of cancer. However, its regulation is complex and dependent on the environment. The expression of Cx43 in triple-negative cancer lesions was analyzed by immunohistochemistry and optical coherence tomography using experimental models and clinical samples. The model of TGFβ1-SMad3-in-αv signal axis was established and verified by experiments. The results show that Cx43 plays a key role in the regulation of triple-negative cancer metastasis. In vivo, over-expressed Cx43 decreased tumor volume and inhibited ITGαV, TGF-β1, Smad3 and N-cadherin expressions, but enhanced the E-cadherin. Cx43 had the lowest expression in the TNBC samples, especially in lymph node metastatic TNBC patients and had a negative correlation with ITG alpha V, TGF-β1 and Smad3.The study demonstrated Cx43 controlled metastatic behavior through TGF-β1 -Smad3-ITG αV signaling axis in MDA-MB-231 cells, providing evidence for Cx43's function in TNBC. The optical image diagnosis method can realize the identification and quantitative evaluation of early cancer triple negative, and provide a new strategy and means for the treatment of cancer triple negative.
间隙连接蛋白 43（Cx43）的异常表达有助于癌症的发生和发展。然而，其调控机制复杂，依赖于环境。通过实验模型和临床样本，采用免疫组织化学和光相干断层扫描技术分析三阴性癌症病变中 Cx43 的表达。通过实验验证了 TGFβ1-SMad3-αv 信号轴模型。结果表明，Cx43 在调节三阴性癌症转移中发挥关键作用。在体内，过表达 Cx43 可降低肿瘤体积并抑制 ITGαV、TGF-β1、Smad3 和 N-钙黏蛋白的表达，而增强 E-钙黏蛋白的表达。Cx43 在 TNBC 样本中的表达最低，特别是在淋巴结转移的 TNBC 患者中，与 ITGαV、TGF-β1 和 Smad3 呈负相关。研究表明 Cx43 通过 TGF-β1-Smad3-ITGαV 信号轴控制 MDA-MB-231 细胞的转移行为，为 Cx43 在 TNBC 中的功能提供了证据。光学图像诊断方法可以实现对早期癌症三阴性的识别和定量评估，为癌症三阴性的治疗提供了新的策略和手段。
