TAF1D promotes tumorigenesis and metastasis by activating PI3K/AKT/mTOR signaling in clear cell renal cell carcinoma

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-09-20 DOI:10.1016/j.cellsig.2024.111425

Xuan Hu , Liang Chen , Tao Liu , Ziyu Wan, Hua Yu, Feng Tang, Jiageng Shi, Zhizhuang Chen, Xinghuan Wang, Zhonghua Yang

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引用次数: 0

Abstract

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor needs more effective treatments. TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D) is a member of the selective factor 1 complex and functions in RNA polymerase I-dependent transcription. Higher TAF1D expression was found in ccRCC tumor tissues and indicated worse survival. Our study aimed to investigate the therapeutic potential of TAF1D in ccRCC. The proliferation and migration of ccRCC cells were significantly inhibited after TAF1D knockdown, while TAF1D overexpressing had opposite effects. Moreover, TAF1D knockdown induced cells to undergo G₀/G₁ cell cycle arrest and blockade of the epithelial-mesenchymal transition (EMT) process. Mechanistically, TAF1D affect the cell cycle and EMT through the PI3K/AKT/mTOR signaling pathway, thereby promoting the proliferation and metastasis of ccRCC cells in vivo and in vitro. The inhibitory effect of TAF1D knockdown could be reverted by the AKT activator SC79 in ccRCC cells, confirming this mechanism. Besides, TAF1D knockdown in ccRCC cells had a sensitizing effect on sunitinib and enhanced tumor cell inhibiting induced by sunitinib. In conclusion, TAF1D may be a promising target for the treatment of ccRCC and for overcoming sunitinib resistance.

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TAF1D 通过激活透明细胞肾细胞癌中的 PI3K/AKT/mTOR 信号促进肿瘤发生和转移。

透明细胞肾细胞癌（ccRCC）是一种需要更有效治疗的恶性肿瘤。TATA 盒结合蛋白相关因子 RNA 聚合酶 I 亚基 D（TAF1D）是选择因子 1 复合物的成员，在 RNA 聚合酶 I 依赖性转录中发挥作用。TAF1D在ccRCC肿瘤组织中表达较高，表明生存率较低。我们的研究旨在探讨 TAF1D 在 ccRCC 中的治疗潜力。TAF1D敲除后，ccRCC细胞的增殖和迁移明显受到抑制，而TAF1D过表达则有相反的效果。此外，TAF1D敲除可诱导细胞发生G0/G1细胞周期停滞，并阻断上皮-间质转化（EMT）过程。从机理上讲，TAF1D通过PI3K/AKT/mTOR信号通路影响细胞周期和EMT，从而促进ccRCC细胞在体内和体外的增殖和转移。在ccRCC细胞中，AKT激活剂SC79可以逆转敲除TAF1D的抑制作用，证实了这一机制。此外，TAF1D在ccRCC细胞中的敲除对舒尼替尼有增敏作用，并能增强舒尼替尼诱导的肿瘤细胞抑制作用。总之，TAF1D可能是治疗ccRCC和克服舒尼替尼耐药性的一个有前景的靶点。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.