The Distinct Roles of Transcriptional Factor KLF11 in Normal Cell Growth Regulation and Cancer as a Mediator of TGF-β Signaling Pathway
Lili Lin, Sven Mahner, Udo Jeschke, Anna Hester
Abstract
KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. KLF11 was initially described as a transforming growth factor-beta (TGF-β) inducible immediate early gene (TIEG). KLF11 promotes the effects of TGF-β on cell growth control by influencing the TGFβ-Smads signaling pathway and regulating the transcription of genes that induce either apoptosis or cell cycle arrest. In carcinogenesis, KLF11 can show diverse effects. Its function as a tumor suppressor gene can be suppressed by phosphorylation of its binding domains via oncogenic pathways. However, KLF 11 can itself also show tumor-promoting effects and seems to have a crucial role in the epithelial-mesenchymal transition process. Here, we review the current knowledge about the function of KLF11 in cell growth regulation. We focus on its transcriptional regulatory function and its influence on the TGF-β signaling pathway. We further discuss its possible role in mediating crosstalk between various signaling pathways in normal cell growth and in carcinogenesis.