Zhou Xiangxiang, Wang Xin
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.
J Cancer Res Clin Oncol. 2015 Jun;141(6):961-9. doi: 10.1007/s00432-014-1788-y. Epub 2014 Aug 3.
The Klotho gene was originally identified as an anti-aging gene in 1997. Recent studies have demonstrated aberrant expression of Klotho in a number of cancers, including breast cancer, lung cancer, hepatocellular carcinoma (HCC), and so on.
A literature search focusing on dysregulation of Klotho and its possible mechanisms in cancer was performed.
Downregulation of Klotho was found in several cancers, such as pancreatic cancer, HCC, and other tumors. Epigenetic modulation, such as promoter methylation and histone deacetylation, also contributed to the dysregulation of Klotho in cancers. Downregulation of Klotho resulted in promoted proliferation and reduced apoptosis of cancer cells. The relevant mechanisms include the fibroblast growth factor signaling, the insulin-like growth factor 1 receptor pathway, and the Wnt/β-catenin signaling pathway. Furthermore, the Klotho protein hopefully provides new insights into cancer target treatment.
1997年,klotho基因最初被鉴定为一种抗衰老基因。最近的研究表明,klotho在包括乳腺癌、肺癌、肝细胞癌(HCC)等多种癌症中存在异常表达。
进行了一项聚焦于klotho失调及其在癌症中可能机制的文献检索。
在胰腺癌、肝癌和其他一些肿瘤等多种癌症中发现了klotho的下调。表观遗传调控,如启动子甲基化和组蛋白去乙酰化,也导致了癌症中klotho的失调。klotho的下调导致癌细胞增殖增加和凋亡减少。相关机制包括成纤维细胞生长因子信号传导、胰岛素样生长因子1受体途径和Wnt/β-连环蛋白信号传导途径。此外,klotho蛋白有望为癌症靶向治疗提供新的见解。