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PNKD Mediates Lactate-Driven Tumor Progression in Clear Cell Renal Cell Carcinoma 期刊论文

编号：

CFBF44577493C23E0F92B301ACF4476D
作者：

Zhang, Xinfang#^[1,2,3]Guo, Wei^[4,5];Yu, Minghui^[6];Wang, Yijia^[7];Cui, Bing^[2,3,8];Zhang, Yaohua^[2,3,8];Yan, Jun*^[1]Wang, Kaichen(王凯臣)*^[6]
语种：

英文
期刊：

HUMAN MUTATION ISSN：1059-7794 2026 年 2026 卷 1 期
收录：
关键词：

clear cell renal cell carcinoma lactate metabolism PI3K-AKT-mTOR signaling PNKD
摘要：

Clear cell renal cell carcinoma (ccRCC) is a metabolically reprogrammed malignancy in which lactate accumulation is increasingly recognized as a functional driver of tumor progression rather than a passive by-product of glycolysis. In this study, we used multiomics data and experiments to reveal lactate-related gene expression differences and identified PNKD as a new metabolic regulator that links lactate production to cancer-promoting signaling. Lactate-related clustering revealed two molecular subtypes with distinct prognostic patterns, immune phenotypes, and tumor mutation burden. A five-gene prognostic signature was established and validated, enabling robust risk stratification across cohorts. Among the signature genes, PNKD exhibited the strongest tumor-associated expression trend and was functionally confirmed to enhance lactate production, accelerate cell-cycle progression, and promote tumor growth. Mechanistically, PNKD activated the PI3K-AKT-mTOR axis, and pharmacological PI3K inhibition reversed PNKD-induced metabolic and proliferative phenotypes in vitro and in vivo. Moreover, spatial colocalization of PNKD and phosphorylated ribosomal protein S6 (p-S6) in xenografts indicated that PNKD-high regions represent metabolically active proliferative niches. These findings establish PNKD as a lactate-driven oncogenic effector and highlight the therapeutic potential of targeting lactate metabolism-signaling crosstalk in ccRCC.
推荐引用方式
GB/T 7714：

Zhang Xinfang,Guo Wei,Yu Minghui, et al. PNKD Mediates Lactate-Driven Tumor Progression in Clear Cell Renal Cell Carcinoma [J].HUMAN MUTATION,2026,2026(1).
APA：

Zhang Xinfang,Guo Wei,Yu Minghui,Wang Yijia,&Wang Kaichen.(2026).PNKD Mediates Lactate-Driven Tumor Progression in Clear Cell Renal Cell Carcinoma .HUMAN MUTATION,2026(1).
MLA：

Zhang Xinfang, et al. "PNKD Mediates Lactate-Driven Tumor Progression in Clear Cell Renal Cell Carcinoma" .HUMAN MUTATION 2026,1(2026).
入库时间：

4/9/2026 9:25:18 PM
更新时间：

4/9/2026 9:25:18 PM

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