Wang X, Zhao J
Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA.
Oncogene. 2007 Jan 18;26(3):456-61. doi: 10.1038/sj.onc.1209796. Epub 2006 Jul 10.
Kruppel-like factor 8 (KLF8) is a member of the family of KLF transcription factors. Several KLF members have been shown to play a role in oncogenesis. We have previously demonstrated that KLF8 mediates cell cycle progression downstream of focal adhesion kinase (FAK) by upregulating cyclin D1. FAK plays a critical role in transformation and tumorigenesis and is aberrantly upregulated in many types of human cancer. Little is known about the function of KLF8 in these regards. Here we provide evidence suggesting a novel role of KLF8 in oncogenic transformation. We show that KLF8 expression is elevated in several types of human cancer cells and primary tumor tissues. Induced expression of ectopic KLF8 causes serum-independent growth and morphological transformation in NIH3T3 cells and enhances anchorage-independent growth of v-Src-transformed cells. In contrast, expression of a dominant-negative mutant of KLF8 dramatically suppresses the transformed phenotypes induced by v-Src. In addition, the KLF8-enhanced transformation in the v-Src cells was prevented by ablating cyclin D1 expression. Overall, these results indicate that KLF8 is required for v-Src-induced transformation and may play a role in tumor progression of human cancer.
Kruppel样因子8（KLF8）是KLF转录因子家族的成员。已有研究表明，多个KLF成员在肿瘤发生过程中发挥作用。我们之前已经证明，KLF8通过上调细胞周期蛋白D1来介导粘着斑激酶（FAK）下游的细胞周期进程。FAK在细胞转化和肿瘤发生中起关键作用，并且在多种人类癌症中异常上调。关于KLF8在这些方面的功能知之甚少。在此，我们提供证据表明KLF8在致癌转化中具有新的作用。我们发现KLF8在多种人类癌细胞和原发性肿瘤组织中表达升高。异位诱导表达KLF8可使NIH3T3细胞实现不依赖血清的生长和形态转化，并增强v-Src转化细胞的非贴壁依赖性生长。相反，KLF8显性负性突变体的表达可显著抑制v-Src诱导的转化表型。此外，通过消除细胞周期蛋白D1的表达可阻止v-Src细胞中KLF8增强的转化。总体而言，这些结果表明KLF8是v-Src诱导的转化所必需的，并且可能在人类癌症的肿瘤进展中发挥作用。
