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Epha2 通过增强 Akt/mtor 信号通路促进人舌鳞癌细胞 Cal-27 的侵袭和迁移。

EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway.

机构信息

Department of Stomatology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Wuhan 430014, China.

出版信息

Biomed Res Int. 2021 Mar 24;2021:4219690. doi: 10.1155/2021/4219690. eCollection 2021.

Abstract

EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.

摘要

EphA2 是 Eph 受体酪氨酸激酶家族的成员,与恶性肿瘤的进展密切相关。EphA2 对口腔鳞状细胞癌(OSCC)的影响尚不清楚。本研究探讨了 EphA2 及 AKT/mTOR 信号通路在 Cal-27 细胞侵袭和迁移中的作用。采用免疫组织化学法检测 EphA2 和 EphA4 在人 OSCC 组织和正常口腔组织中的表达。构建 EphA2 过表达和 EphA2 敲低 Cal-27 细胞系,用 AKT 抑制剂(MK2206)和 mTOR 抑制剂(RAD001)处理细胞。采用 qRT-PCR 检测 EphA2 的表达,MTT 法评估细胞增殖,划痕和 Transwell 实验检测细胞迁移和侵袭,Hoechst 33258 染色评估细胞形态和凋亡。Western blot 检测与 AKT/mTOR 信号通路、细胞周期和伪足侵袭相关蛋白的表达。EphA2 和 EphA4 在临床人 OSCC 中高表达。EphA2 过表达促进 Cal-27 细胞的增殖、迁移和侵袭,抑制细胞周期阻滞和凋亡,并增强 AKT/mTOR 信号通路的活性。AKT 抑制剂(MK2206)和 mTOR 抑制剂(RAD001)逆转 EphA2 过表达对 Cal-27 细胞生物学行为的影响。EphA2 通过增强 AKT/mTOR 信号通路促进 Cal-27 人 OSCC 细胞的侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f0/8016562/ada8c48dca16/BMRI2021-4219690.001.jpg

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