KLF9 Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin-{alpha}6 Inhibition [Gene Regulation]

October 6th, 2014 by Ying, M., Tilghman, J., Wei, Y., Guerrero-Cazares, H., Quinones-Hinojosa, A., Ji, H., Laterra, J.

It is increasingly important to understand the molecular basis for the plasticity of neoplastic cells and their capacity to transition between differentiated and stem-like phenotypes. Kruppel-like factor-9 (KLF9), a member of the large KLF transcription factor family, has emerged as a regulator of oncogenesis, cell differentiation and neural development; however, the molecular basis for KLF9's diverse contextual functions remains unclear. This paper focuses on the functions of KLF9 in human glioblastoma stem-like cells. We establish for the first time a genome-wide map of KLF9-regulated targets in human glioblastoma stem-like cells, and show that KLF9 functions as a transcriptional repressor and thereby regulates multiple signaling pathways involved in oncogenesis and stem cell regulation. A detailed analysis of one such pathway, integrin signaling, shows that the capacity of KLF9 to inhibit glioblastoma cell stemness and tumorigenicity requires ITGA6 repression. These findings enhance our understanding of the transcriptional networks underlying cancer cell stemness and differentiation, and provide new regulatory mechanisms applicable to cancer therapeutics.