KLF8 transcription factor participates in oncogenic transformation.
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.
Wang
X
X
Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA.
Zhao
J
J
D000818:Animals; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D041681:NIH 3T3 Cells; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C507402:KLF8 protein, human; C475812:Klf8 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D019938:Cyclin D1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)