基诺美
癌症研究
细胞周期
生物
激酶
肾细胞癌
酪氨酸激酶
细胞凋亡
信号转导
细胞生物学
医学
内科学
生物化学
作者
Derek J. Essegian,Valery Chávez,Floritza Bustamante,Stephan C. Schürer,Jaime R. Merchan
出处
期刊:iScience
[Cell Press]
日期:2022-11-17
卷期号:25 (12): 105621-105621
被引量:2
标识
DOI:10.1016/j.isci.2022.105621
摘要
Renal cell carcinoma (RCC) is a fatal disease when advanced. While immunotherapy and tyrosine kinase inhibitor-based combinations are associated with improved survival, the majority of patients eventually succumb to the disease. Through a comprehensive pan-cancer, pan-kinome analysis of the Cancer Genome Atlas (TCGA), pregnancy-upregulated non-ubiquitous calcium-calmodulin-dependent kinase (PNCK), was identified as the most differentially overexpressed kinase in RCC. PNCK overexpression correlated with tumor stage, grade and poor survival. PNCK overexpression in RCC cells was associated with increased CREB phosphorylation, increased cell proliferation, and cell cycle progression. PNCK down-regulation, conversely, was associated with the opposite, in addition to increased apoptosis. Pathway analyses in PNCK knockdown cells showed significant down-regulation of hypoxia and angiogenesis pathways, as well as the modulation of the cell cycle, DNA damage, and apoptosis pathways. These results demonstrate for the first time the biological role of PNCK, an understudied kinase, in RCC and validate PNCK as a druggable target.
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