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CCR7 mediates human breast cancer cell invasion migration by inducing epithelial–mesenchymal transition and suppressing apoptosis through AKT pathway

机译:CCR7通过诱导上皮-间质转化并通过AKT途径抑制细胞凋亡来介导人类乳腺癌细胞的侵袭迁移

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摘要

Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits style="fixed-case">CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and style="fixed-case">EMT. Moreover, we demonstrated that style="fixed-case">CCL19‐induced style="fixed-case">AKT phosphorylation; however, style="fixed-case">CCR7 si style="fixed-case">RNA suppressed style="fixed-case">CCL19‐induced style="fixed-case">AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that style="fixed-case">CCL19/ style="fixed-case">CCR7 axis regulated style="fixed-case">EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of style="fixed-case">AKT signal pathway. Our results suggested that style="fixed-case">CCR7 may regard as a therapeutic target for the breast cancer treatment.
机译:趋化因子和趋化因子受体在肿瘤进展中起关键作用。在这里,我们认为CCR7可能诱导乳腺癌的侵袭,迁移和上皮-间质转化(EMT)过程。在这项研究中,分别使用CCL19和小干扰RNA(CCR7 siRNA)处理人乳腺癌MCF-7和MDA-MB-231细胞,以激活和抑制CCR7。细胞侵袭和transwell分析用于检测CCR7对侵袭和迁移的影响。结果表明,CCL19通过诱导EMT介导细胞侵袭和迁移,同时下调E-钙粘蛋白和N-钙粘蛋白和波形蛋白的水平。另一方面,CCR7的敲低揭示了与CCL19组和对照组相比的变化。抑制CCR7抑制 style =“ fixed-case”> CCL 19诱导的乳腺癌细胞增殖,细胞周期,迁移,侵袭和 style =“ fixed-case”> EMT 。此外,我们证明了 style =“ fixed-case”> CCL 19-诱导的 style =“ fixed-case”> AKT 磷酸化;但是, style =“ fixed-case”> CCR 7 si style =“ fixed-case”> RNA 抑制了 style =“ fixed-case”> CCL 19诱导的 style =“ fixed-case”> AKT 磷酸化,是肿瘤转移的关键调节因子。总之,所有发现均表明, style =“ fixed-case”> CCL 19 / style =“ fixed-case”> CCR 7轴可调节 style =“ fixed-case “> EMT 在乳腺癌细胞中的进展,并通过激活 style =” fixed-case“> AKT 信号通路来介导肿瘤细胞的侵袭和迁移过程。我们的结果表明, style =“ fixed-case”> CCR 7可能被视为乳腺癌的治疗靶标。

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