联系我们

CONTACT US

币安交易所网址
地址:厦门火炬高新区(翔安)产业区翔星路98号强业楼406室

电 话:0592-5771844 

手 机:15860722185

邮 箱:63706983@qq.com

Nat Com:华东师范大学王传贵课题组发现新肿瘤抑制因子

作者:Nature Communications 发布时间:2015-10-19

2015年10月6日,Nature出版集团旗下子刊《Nature Communications》期刊上在线发表了华东师范大学生命科学学院生命医学研究所王传贵课题组报道了肿瘤基因组不稳定的发生机制,原创性发现了一个新肿瘤抑制因子。研究论文题为“Loss of KLF14 triggers centrosome amplification and tumorigenesis”,华东师范大学生命科学学院学生范光建(Guangjian Fan)为第一作者,王传贵研究员为论文通讯作者。

基因组不稳定是肿瘤标志性分子特征之一,在肿瘤发生、诊断和治疗等方面有重要意义。揭示肿瘤基因组不稳定的形成机制,对肿瘤发生发展分子研究及促生有效临床诊断和治疗手段,都至关重要。另外,基因组不稳定与肿瘤发生的因果关系,也是学术界的前沿热点问题。

该论文研究发现,脂代谢调控热点基因KLF4(也被冠名为脂代谢/肥胖 “总开关”),有维持基因组稳定和抵抗肿瘤发生的作用。动物实验发现,KLF14缺失可诱发中心体过度复制、基因组不稳定和多种肿瘤形成;临床研究发现,KLF14转录和蛋白表达在多种人肿瘤组织中显著降低;分子上,KLF14可通过转录抑制中心体复制关键基因Plk4,实现细胞有丝分裂和基因组稳定维护。 另外,该论文还发现,KLF14表达增高可导致细胞周期M期阻滞并诱发有丝分裂灾变性细胞死亡(恶性肿瘤治疗新方向)。该研究原创性揭示KLF14是一新的肿瘤抑制因子,该基因有望成为肿瘤诊疗和抗肿瘤药物研发的新靶标。

原文链接:

Loss of KLF14 triggers centrosome amplification and tumorigenesis

原文摘要:

Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinically, KLF14 transcription is significantly downregulated, wheras Plk4 transcription is upregulated in multiple types of cancers, and there exists an inverse correlation between KLF14 and Plk4 protein expression in human breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a mechanism leading to centrosome amplification and tumorigenesis. On the other hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our findings identify KLF14 as a tumour suppressor and highlight its potential as biomarker and therapeutic target for cancer.

文章来源:生物帮