Krüppel‐like factor 6 interferes with cellular transformation induced by the H‐ras oncogene. Issue 12 (11th September 2014)

• Record Type: Journal Article
• Authors: Trucco, Lucas Daniel; Andreoli, Verónica; Núñez, Nicolás Gonzalo; Maccioni, Mariana; Bocco, José Luis
• Is Part Of: FASEB journal. Volume 28:Issue 12(2014)
• Page Start: 5262
• Page End: 5276
• Publication Date: 2014-09-11
• Subjects: tumor suppressor -- c‐Jun N‐terminal kinase -- p21; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.14-251884
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : KLF6 is a member of the Krüppel‐like factor family of transcription factors, with diverse roles in the regulation of cell physiology, including proliferation, signal transduction, and apoptosis. Mutations or down‐regulation of KLF6 have been described in several human cancers. In this work, we found that KLF6‐knockdown resulted in the formation of transformed foci and allowed the spontaneous conversion of NIH3T3 cells to a tumorigenic state. We further assessed the role of KLF6 in the context of oncogenic Ras. We showed that KLF6 was up‐regulated by H‐Ras G12V expression in a Jun N‐terminal kinase (JNK)‐dependent manner, correlated with enhanced klf6 promoter activity. We found that ectopic KLF6 expression induced a G1‐phase cell cycle arrest, thereby decreasing the cell proliferation rate. In addition, constitutive KLF6 expression impaired H‐Ras G12V ‐mediated loss of density‐dependent growth inhibition and anchorage‐independent growth. Moreover, growth of H‐Ras G12V driven tumors was reduced in mice challenged with cells stably expressing KLF6. KLF6 expression correlated with the up‐regulation of p21, whereas neither p53 induction nor apoptotic cell death was detected. Further, p21 knockdown impaired KLF6‐induced cell cycle arrest. These findings provide novel evidence highlighting KLF6 function in response to malignant transformation, suggesting the relevance of KLF6 in controlling cell proliferation and hindering tumorigenesis. Trucco, L. D., Andreoli, V., Núñez, N. G., Maccioni, M., Bocco, J. L. Krüppel‐like factor 6 interferes with cellular transformation induced by the H‐ ras oncogene. FASEB J. 28, 5262–5276 (2014). www.fasebj.org