Centromere protein K enhances the activation of YAP1/TAZ signal cascade to drive the progression of clear cell renal cell carcinoma.

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Toxicology and applied pharmacology Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1016/j.taap.2024.117181
Ning Nan
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引用次数: 0

Abstract

Centromere protein K (CENPK) is a newly identified malignancy-related gene that exhibits differential expression in various cancers and plays a crucial role in carcinogenesis. However, it remains uncertain whether CENPK is involved in clear cell renal cell carcinoma (ccRCC). This work aimed to unveil the expression, clinical significance, biological functions, and regulatory mechanisms of CENPK in ccRCC. Through analysis of RNA-seq data obtained from TCGA, a high expression pattern of CENPK was identified in ccRCC, which was found to be associated with pathologic stage, histologic grade, and clinical outcome. The enrichment of CENPK in ccRCC was further verified through the analysis of clinical samples. By conducting cellular functional experiments, we showed an inhibitory effect of CENPK knockdown on the malignant behavior of ccRCC cells. GSEA revealed a close relationship between CENPK and the Hippo-YAP1/TAZ signal cascade. The following experiments demonstrated that the activation of YAP1/TAZ was strongly inhibited by CENPK knockdown, and this change was accompanied by a decrease in the levels of CTGF and CYR61. Blockade of the MST1/2-LATS1/2 axis reversed the suppressive impact of CENPK knockdown on YAP1/TAZ. The tumor-promoting impact observed upon CENPK overexpression was diminished in YAP1 knockout cells. Notably, ccRCC cells with reduced CENPK expression exhibited a diminished capability to form tumors in nude mice. This report highlights the importance of CENPK in ccRCC and sheds new light on the underlying mechanism of this cancer type. Therefore, CENPK has the potential to serve as a viable candidate target for treating ccRCC.

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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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