Wen Zhengwei, Liang Yingfan, Deng Shengming, Zou Lilin, Xie Xiaofan, Yang Jifeng, Wu Yiwei
Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
Oncol Lett. 2019 Jun;17(6):4835-4842. doi: 10.3892/ol.2019.10175. Epub 2019 Mar 21.
The talin proteins are a key component of the extracellular matrix-integrin-cytoskeleton system, and our previous study suggested that talin2 contributes to the tumor invasion and metastasis processes regulated by the tumor microenvironment. In the present study, the specific effects of talin2 on the invasive ability of breast cancer cells, as well as the underlying mechanism, were investigated by creating two MDA-MB-231 cell lines with stable talin2 knockdown by specific RNA interference. Initially, it was confirmed that the expression levels of talin2 in human breast cancer tissues were upregulated compared with in normal adjacent tissues. Subsequently, invasion and wound healing assays revealed that depletion of talin2 in MDA-MB-231 cells decreased their migratory and invasive abilities. Western blot analysis demonstrated that knockdown of talin2 in MDA-MB-231 cells caused marked downregulation of the tumor microenvironment markers hypoxia-inducible factor 1α, phosphorylated ribosomal protein S6 kinase, phosphorylated protein kinase B and phosphorylated mechanistic target of rapamycin. Furthermore, knockdown of talin2 decreased the basal contents of glucose and lactic acid in the breast cancer cell line. In conclusion, the findings of the present study demonstrated that talin2 knockdown may inhibit the invasive ability of human breast cancer MDA-MB-23l cells via alterations in the tumor microenvironment.
踝蛋白是细胞外基质-整合素-细胞骨架系统的关键组成部分,我们之前的研究表明,踝蛋白2有助于肿瘤微环境调节的肿瘤侵袭和转移过程。在本研究中,通过特异性RNA干扰创建了两个稳定敲低踝蛋白2的MDA-MB-231细胞系,研究了踝蛋白2对乳腺癌细胞侵袭能力的具体影响及其潜在机制。最初,证实与相邻正常组织相比,人乳腺癌组织中踝蛋白2的表达水平上调。随后,侵袭和伤口愈合试验表明,MDA-MB-231细胞中踝蛋白2的缺失降低了它们的迁移和侵袭能力。蛋白质印迹分析表明,MDA-MB-231细胞中踝蛋白2的敲低导致肿瘤微环境标志物缺氧诱导因子1α、磷酸化核糖体蛋白S6激酶、磷酸化蛋白激酶B和磷酸化雷帕霉素机制靶点的显著下调。此外,踝蛋白2的敲低降低了乳腺癌细胞系中葡萄糖和乳酸的基础含量。总之,本研究结果表明,敲低踝蛋白2可能通过改变肿瘤微环境来抑制人乳腺癌MDA-MB-231细胞的侵袭能力。