受体型蛋白酪氨酸磷酸酶 Epsilon（PTPRE）通过激活 AKT 和 ERK1/2 信号通路在甲状腺癌中发挥致癌作用。

Receptor Type Protein Tyrosine Phosphatase Epsilon (PTPRE) Plays an Oncogenic Role in Thyroid Carcinoma by Activating the AKT and ERK1/2 Signaling Pathway.

机构信息

Otolaryngology Head and Neck Surgery Research Institute, Shanxi Medical University, Taiyuan, 030001, China.

Department of Head and Neck Surgery, Shanxi Province Cancer Hospital, Taiyuan, 030001, China.

出版信息

Curr Cancer Drug Targets. 2023;23(6):471-481. doi: 10.2174/1568009623666230118111745.

DOI:10.2174/1568009623666230118111745

PMID:36654463

Abstract

BACKGROUND

Thyroid carcinoma (TC) is a common malignant tumor in human and its incidence has been increasing in recent years. Studies have shown that receptor type protein tyrosine phosphatase epsilon (PTPRE) is a key regulator of tumorigenesis in cancer progression, but its role in TC has not been revealed.

OBJECTIVE

Here, in this work, we explored the essential role of PTPRE in TC progression.

METHODS

The expression of PTPRE in TC clinical samples and cell lines was detected by RT-qPCR and Western blot. Cell proliferation was measured by MTT and cell cycle analysis. Cell migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed by wound healing, transwell, and immunofluorescent staining assays. AKT and ERK1/2 signaling pathway related protein level was analyzed by Western blot.

RESULTS

PTPRE was highly expressed in TC clinical samples and cell lines, especially anaplastic thyroid carcinoma (ATC). High level of PTPRE was associated with tumor size and TNM stage. Upregulated PTPRE promoted cell proliferation, and enhanced the migration, invasion and EMT of TC cells, whereas the knockdown of PTPRE suppressed these behaviors. Importantly, we confirmed that the AKT and ERK1/2 signaling pathways were activated by PTPRE, reflected by the enhanced protein level of phosphorylated AKT and ERK1/2.

CONCLUSION

Accordingly, we indicated that PTPRE plays an oncogenic role in TC progression via activating the AKT and ERK1/2 signaling pathway. These findings indicated that modulation of PTPRE expression may as a potential strategy to interfere with the progression of TC.

摘要

背景

甲状腺癌（TC）是人类常见的恶性肿瘤，近年来其发病率呈上升趋势。研究表明，受体型蛋白酪氨酸磷酸酶 epsilon（PTPRE）是癌症进展中肿瘤发生的关键调节因子，但它在 TC 中的作用尚未被揭示。

目的

在本研究中，我们探讨了 PTPRE 在 TC 进展中的重要作用。

方法

通过 RT-qPCR 和 Western blot 检测 TC 临床样本和细胞系中 PTPRE 的表达。通过 MTT 和细胞周期分析测定细胞增殖。通过划痕愈合、Transwell 和免疫荧光染色实验分析细胞迁移、侵袭和上皮-间充质转化（EMT）。通过 Western blot 分析 AKT 和 ERK1/2 信号通路相关蛋白水平。

结果

PTPRE 在 TC 临床样本和细胞系中高度表达，尤其是间变性甲状腺癌（ATC）。高水平的 PTPRE 与肿瘤大小和 TNM 分期相关。上调的 PTPRE 促进 TC 细胞的增殖，并增强其迁移、侵袭和 EMT 能力，而 PTPRE 的敲低则抑制了这些行为。重要的是，我们证实 PTPRE 通过激活 AKT 和 ERK1/2 信号通路来激活 AKT 和 ERK1/2 信号通路，这反映在磷酸化 AKT 和 ERK1/2 的蛋白水平增强上。