文章：

糖尿病条件下乳腺癌细胞的细胞结构：调控激酶——Rho激酶与黏着斑激酶的作用

Cytoarchitecture of Breast Cancer Cells under Diabetic Conditions: Role of Regulatory Kinases—Rho Kinase and Focal Adhesion Kinase

原文发布日期：15 September 2024

DOI: 10.3390/cancers16183166

类型: Article

开放获取: 是

英文摘要：

Diabetes greatly reduces the survival rates in breast cancer patients due to chemoresistance and metastasis. Reorganization of the cytoskeleton is crucial to cell migration and metastasis. Regulatory cytoskeletal protein kinases such as the Rho kinase (ROCK) and focal adhesion kinase (FAK) play a key role in cell mobility and have been shown to be affected in cancer. It is hypothesized that diabetes/high-glucose conditions alter the cytoskeletal structure and, thus, the elasticity of breast cancer cells through the ROCK and FAK pathway, which can cause rapid metastasis of cancer. The aim of the study was to investigate the role of potential mediators that affect the morphology of cancer cells in diabetes, thus leading to aggressive cancer. Breast cancer cells (MDA-MB-231 and MCF-7) were treated with 5 mM glucose (low glucose) or 25 mM glucose (high glucose) in the presence of Rho kinase inhibitor (Y-27632, 10 mM) or FAK inhibitor (10 mM). Cell morphology and elasticity were monitored using atomic force microscopy (AFM), and actin staining was performed by fluorescence microscopy. For comparative study, normal mammary breast epithelial cells (MCF-10A) were used. It was observed that high-glucose treatments modified the cytoskeleton of the cells, as observed through AFM and fluorescence microscopy, and significantly reduced the elasticity of the cells. Blocking the ROCK or FAK pathway diminished the high-glucose effects. These changes were more evident in the breast cancer cells as compared to the normal cells. This study improves the knowledge on the cytoarchitecture properties of diabetic breast cancer cells and provides potential pathways that can be targeted to prevent such effects.

摘要翻译： 

糖尿病通过化疗耐药和转移显著降低乳腺癌患者的生存率。细胞骨架重组对细胞迁移和转移至关重要。调节性细胞骨架蛋白激酶如Rho激酶（ROCK）和黏着斑激酶（FAK）在细胞运动性中起关键作用，并已被证明在癌症中受到影响。研究假设糖尿病/高血糖条件通过ROCK和FAK途径改变细胞骨架结构，从而影响乳腺癌细胞的弹性，可能导致癌症快速转移。本研究旨在探讨影响糖尿病中癌细胞形态的潜在介质的作用，从而导致侵袭性癌症。在Rho激酶抑制剂（Y-27632，10 mM）或FAK抑制剂（10 mM）存在下，用5 mM葡萄糖（低葡萄糖）或25 mM葡萄糖（高葡萄糖）处理乳腺癌细胞（MDA-MB-231和MCF-7）。使用原子力显微镜（AFM）监测细胞形态和弹性，并通过荧光显微镜进行肌动蛋白染色。为进行比较研究，使用了正常乳腺上皮细胞（MCF-10A）。通过AFM和荧光显微镜观察发现，高葡萄糖处理改变了细胞的细胞骨架，并显著降低了细胞的弹性。阻断ROCK或FAK途径减弱了高葡萄糖的影响。与正常细胞相比，这些变化在乳腺癌细胞中更为明显。本研究增进了对糖尿病乳腺癌细胞结构特性的认识，并提供了可靶向预防此类效应的潜在途径。

原文链接：

Cytoarchitecture of Breast Cancer Cells under Diabetic Conditions: Role of Regulatory Kinases—Rho Kinase and Focal Adhesion Kinase