MAPK/ERK通路
癌变
癌症研究
生物
激酶
肺癌
细胞生长
癌症
细胞周期
磷酸化
蛋白激酶A
分子生物学
细胞生物学
医学
内科学
生物化学
遗传学
作者
Minh‐Hue Nguyen,Junkichi Koinuma,Koji Ueda,Tomoo Ito,Eiju Tsuchiya,Yusuke Nakamura,Yataro Daigo
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2010-06-30
卷期号:70 (13): 5337-5347
被引量:74
标识
DOI:10.1158/0008-5472.can-09-4372
摘要
Abstract We analyzed the gene expression profiles of clinical lung carcinomas using a cDNA microarray containing 27,648 genes or expressed sequence tags, and identified CDCA5 (cell division cycle associated 5) to be upregulated in the majority of lung cancers. Tumor tissue microarray analysis of 262 non–small cell lung cancer patients revealed that CDCA5 positivity was an independent prognostic factor for lung cancer patients. Suppression of CDCA5 expression with siRNAs inhibited the growth of lung cancer cells; concordantly, induction of exogenous expression of CDCA5 conferred growth-promoting activity in mammalian cells. We also found that extracellular signal-regulated kinase (ERK) kinase phosphorylated CDCA5 at Ser79 and Ser209 in vivo. Exogenous expression of phospho-mimicking CDCA5 protein whose Ser209 residue was replaced with glutamine acid further enhanced the growth of cancer cells. In addition, functional inhibition of the interaction between CDCA5 and ERK kinase by a cell-permeable peptide corresponding to a 20-amino-acid sequence part of CDCA5, which included the Ser209 phosphorylation site by ERK, significantly reduced phosphorylation of CDCA5 and resulted in growth suppression of lung cancer cells. Our data suggest that transactivation of CDCA5 and its phosphorylation at Ser209 by ERK play an important role in lung cancer proliferation, and that the selective suppression of the ERK-CDCA5 pathway could be a promising strategy for cancer therapy. Cancer Res; 70(13); 5337–47. ©2010 AACR.
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