Onconesis and tumor suppression mechanisms
“FunctionalAnalysis of the Transcription Factor KLF6 in the Control of Cell Proliferation and Oncogenesis”
The transcription factor KLF6 (Krüppel-likeFactor6) was identified in our laboratory as a regulator of expression of genes encoding PSG proteins (Pregnancy-Specific Glycoproteins).
Mutations or expression defects in klf6 gene are associated with the development of different types of cancer in humans, suggesting a role of KLF6 as tumor suppressor.
Results from our group demonstrated a new mechanism of KLF6 in reducing cell proliferation involving the degradation of the proto-oncoprotein c-Jun. Furthermore, KLF6 is capable of reducing tumor generation in vivo triggered by mutated Ras oncogene (mutations in Ras oncogene are present in more than 30% of human cancers). These results correlate with cell cycle arrest in G1 through increased expression of p21(CIPI/WAF1).In this context, neither the induction of p53 nor apoptotic cell death were detected. Interestingly, this cytostatic response of KLF6 correlates directly with apoptosis resistance caused by DNA-damaging chemotherapy drugs used in cancer treatment. Then, demonstrating that KLF6 has the ability to hinder Ras-induced tumorigenesis, which involved a marked arrest in cell cycle progression, supports a relevant role of KLF6 as a tumor suppressor.