Estrogen Receptor alpha depletion affects the biomechanical properties and cytoskeleton rearrangements in breast cancer cells
Estrogen Receptor alpha depletion affects the biomechanical properties and cytoskeleton rearrangements in breast cancer cells
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雌激素受体α耗竭影响乳腺癌的生物力学特性和细胞骨架重排
DOI：
10.1016/j.bbrc.2020.02.030
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发表时间：
2020
影响因子：
3.1
通讯作者：
Linyan Zhu
中科院分区：
文献类型：
--
作者：
Chongyu Zhao;Xiuying Hou;Zihan Peng;Xiaoxue Sun;Enze Li;Haifeng Yang;Yuanzhi Lu;Linyan Zhu
雌激素受体α (Estrogen Receptor α, ERα)影响肿瘤的形态，与肿瘤的生物力学特性和细胞骨架蛋白密切相关。近年来，研究人员发现生物力学性质和细胞骨架蛋白与肿瘤的发生发展密切相关，生物力学性质可作为肿瘤发生发展和耐药的标志物。ERα表达状态与生物力学特性、细胞骨架蛋白之间的关系尚不清楚。在本研究中，我们发现他莫昔芬耐药乳腺癌细胞（MCF-7/TamR）在他莫昔芬耐药诱导过程中改变了细胞形态，缺乏ERα表达。为了确定这种变化是否受到ERα表达的影响，我们用ERα siRNA构建了另一个ERα缺失模型（MCF-7/ERα siRNA），并使用原子力显微镜（AFM）检测形态学和生物物理变化。结果表明，ERα表达缺失的细胞粗糙度和杨氏模量显著升高，细胞骨架蛋白（F-actin、FLNA、α-微管蛋白）重排，细胞骨架调节蛋白Rho （Rac1、CDC42）降低。我们的研究结果表明，ERα缺失会影响乳腺癌细胞的生物力学特性，这与细胞骨架蛋白重排和Rho蛋白减少有关。
Estrogen Receptor alpha (ERα) affects the morphology of tumors, which is closely related to the biomechanical properties and the cytoskeletal proteins. In recent years, researchers have found that biomechanical properties and cytoskeletal proteins are closely related to the occurrence and development of tumors and that biomechanical properties can be used as markers for tumor development and drug resistance. The relationship between ERα expression status and biomechanical properties, cytoskeletal proteins is not known. In this study, we found that tamoxifen-resistant breast cancer cells (MCF-7/TamR) altered cell morphology and lacked of ERα expression during the process of the Tamoxifen resistance induction. To determine whether this change was influenced by ERα expression, we transiently constructed another ERα depleted model with ERα siRNA (MCF-7/ERα siRNA) and used atomic force microscope (AFM) to detect morphological and biophysical changes. The results indicated that the roughness and Young’s modulus of ERα expression depleted cells were significantly increased, accompanied by rearrangement of the cytoskeletal proteins (F-actin, FLNA, α-tubulin) and the cytoskeletal regulatory protein Rho (Rac1, CDC42) decreased. Our results have demonstrated that ERα depletion affects the biomechanical properties of breast cancer cells, which are related to cytoskeletal protein rearrangement and Rho protein decreased.