Abstract 1656: Mouse embryonic fibroblasts null for krüppel-like factor 4 show reduced autophagy and elevated mTOR activity

Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor named for its homology to the Drosophila protein Krüppel. KLF4 negatively regulates cell-cycle progression and, cell proliferation, and is a known tumor suppressor in certain cancers. Autophagy, or self-eating, is a process through which intracellular aggregates can be degraded and their components recycled. The role of autophagy in cancer appears to be context dependent. In pre-cancerous tissue, autophagy may serve a protective purpose, removing cytotoxic aggregates and promoting a healthy intracellular environment. In cancerous tissue, however, autophagy may allow cancer cell survival. Previous studies examining gene expression in WT (KLF4+/+) and KLF4 null (KLF4-/-) mouse embryonic fibroblasts (MEFs) revealed autophagy related gene expression to be downregulated in KLF4-/- MEFs. In order to evaluate whether KLF4 is important in autophagy, we examined microtubule associated protein-1 light chain 3 protein (LC3, a marker of autophagy) and a downstream target of mTOR (p70S6K, a marker of autophagy inhibition) in KLF4+/+ and KLF4-/- MEFs. Our results show that levels of LC3 are reduced and levels of p70S6K are elevated in both KLF4-/- MEFs and MEFs in which KLF4 has been transiently silenced. Rapamycin treatment, which inhibits mTOR activity, fails to restore autophagy in KLF4 null MEFs. Collectively, these findings suggest that KLF4 may negatively regulate mTOR activity and that KLF4 may also be necessary for induction of autophagy either downstream or entirely independent of mTOR. Citation Format: Hagos Engda, Elise DeRoo. Mouse embryonic fibroblasts null for krüppel-like factor 4 show reduced autophagy and elevated mTOR activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1656. doi:10.1158/1538-7445.AM2013-1656 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.