ΔNp63α promotes cigarette smoke-induced renal cancer stem cell activity via the Sonic Hedgehog pathway.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-01 eCollection Date: 2024-01-01 DOI:10.1590/1678-4685-GMB-2023-0347

Yuxiang Zhao, Nannan Ma, Wanngyu Wu, Ying Wu, Wenbo Zhang, Weiwei Qian, Xin Sun, Tao Zhang

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引用次数: 0

Abstract

Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway.

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ΔNp63α通过Sonic Hedgehog途径促进香烟烟雾诱导的肾癌干细胞活性

香烟烟雾（CS）已被公认为是肾细胞癌（RCC）的主要致癌因素。以前曾描述过 CS 对肾癌干细胞（RCSCs）的刺激作用。音速刺猬（SHH）通路在癌症干细胞（CSCs）的自我更新、细胞生长、耐药性、转移和复发中发挥着重要作用。肾癌相关基因ΔNp63α在肾上皮组织中高表达，并促成了肿瘤的RCSCs特征。本研究旨在通过一系列体内和体外研究，阐明ΔNp63α和SHH通路对CS诱导的RCSCs活性的作用。研究表明，在肾癌组织中，吸烟者的ΔNp63α和RCSCs标记物的表达高于非吸烟者。在肿瘤球形成试验中，RCSCs 被有效富集。此外，CS 增加了 RCSCs 标志物的表达，并提高了体外和体内形成球体的能力。此外，SHH通路被激活，而专门的抑制剂减轻了CS对RCSCs的促进作用。ΔNp63α激活了SHH通路，促进了CS诱导的RCSCs活性增强。这些研究结果表明，ΔNp63α通过SHH通路对CS诱导的RCSCs的活性进行正向调节。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.