TFAP2C Affects PI3K/AKT/mTOR Pathway-Mediated EMT for Glioblastoma Development Through Transcriptional Regulation.

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International Pub Date : 2025-07-16 DOI:10.1002/cbin.70062

Shilin Li, Kebo Liu, Xiaoyang Li, Hao Zi, Kaiyuan Jiang

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引用次数: 0

Abstract

Transcription factor AP-2 gamma (TFAP2C) plays a pro-cancer role in various malignancies. Yet, the action of TFAP2C in glioblastoma (GBM) is unknown. This study aimed to investigate the effects of TFAP2C in GBM and the potential mechanism. TFAP2C knockdown in GBM cell lines was employed to examine its impact on cell proliferation, migration, and invasion (PMI), as well as epithelial-mesenchymal transition (EMT) development, and its association with the PI3K/AKT/mTOR (PAM) pathway by co-overexpressing PI3K or SC79 treatment (AKT agonist). The binding of TFAP2C and the PI3K promoter was predicted and validated. Finally, the above effects and mechanisms were verified in in vivo animal experiments. TFAP2C expression was strikingly heightened in human GBM cell lines and showed a negative correlation with patient survival. TFAP2C silencing inhibited GBM cell PMI, N-cadherin and Vimentin expression, and the PAM pathway, and activated E-cadherin and ZO-1 expression. Overexpression of PI3K or SC79 treatment reversed the above changes, suggesting that TFAP2C promotes GBM cell PMI and EMT via the PAM pathway. Mechanistically, TFAP2C binds to the promoter of PI3K and regulates PI3K transcription. Finally, the in vitro results were further validated in animal experiments. In conclusion, TFAP2C promotes PI3K transcription through direct binding to the promoter of PI3K and activates the PAM pathway to promote GBM proliferation and EMT, providing a potential therapeutic target for GBM.

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TFAP2C通过转录调控影响PI3K/AKT/mTOR通路介导的EMT对胶质母细胞瘤的发展。

转录因子AP-2 γ (TFAP2C)在多种恶性肿瘤中起促癌作用。然而，TFAP2C在胶质母细胞瘤（GBM）中的作用尚不清楚。本研究旨在探讨TFAP2C在GBM中的作用及其可能的机制。研究人员利用TFAP2C敲低GBM细胞系来检测其对细胞增殖、迁移和侵袭（PMI）以及上皮-间质转化（EMT）发育的影响，并通过共过表达PI3K或SC79处理（AKT激动剂）来检测其与PI3K/AKT/mTOR （PAM）通路的关联。预测并验证了TFAP2C与PI3K启动子的结合。最后，通过动物体内实验验证了上述作用和机制。TFAP2C在人GBM细胞系中的表达显著升高，并与患者生存率呈负相关。TFAP2C沉默抑制GBM细胞PMI、N-cadherin、Vimentin表达及PAM通路，激活E-cadherin、ZO-1表达。PI3K过表达或SC79处理逆转了上述变化，提示TFAP2C通过PAM途径促进GBM细胞PMI和EMT。在机制上，TFAP2C结合PI3K的启动子并调节PI3K的转录。最后，在动物实验中进一步验证体外实验结果。综上所述，TFAP2C通过直接结合PI3K启动子促进PI3K转录，激活PAM通路促进GBM增殖和EMT，为GBM提供了潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biology International 生物-细胞生物学

CiteScore

7.60

自引率

0.00%

发文量

208

审稿时长

1 months

期刊介绍： Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.