Essential role of KLF5 transcription factor in cell proliferation and differentiation and its implications for human diseases

Abstract

KLF5 (Kruppel-like factor 5) is a basic transcription factor binding to GC boxes at a number of gene promoters and regulating their transcription. KLF5 is expressed during development and, in adults, with higher levels in proliferating epithelial cells. The expression and activity of KLF5 are regulated by multiple signaling pathways, including Ras/MAPK, PKC, and TGFbeta, and various posttranslational modifications, including phosphorylation, acetylation, ubiquitination, and sumoylation. Consistently, KLF5 mediates the signaling functions in cell proliferation, cell cycle, apoptosis, migration, differentiation, and stemness by regulating gene expression in response to environment stimuli. The expression of KLF5 is frequently abnormal in human cancers and in cardiovascular disease-associated vascular smooth muscle cells (VSMCs). Due to its significant functions in cell proliferation, survival, and differentiation, KLF5 could be a potential diagnostic biomarker and therapeutic target for cancer and cardiovascular diseases.

Krüppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression

“…Sp1 and AP2 were important for regulating the expression of KRT during epithelial cell differentiation (37,38). KLF5 played an essential role in the differentiation and homeostasis of epithelial cells, smooth muscle cells and adipocytes by regulating the expression of KRT5, SM22␣, peroxisome proliferator-activated receptor ␥ and others (39,40). Our previous results showed that KLF4 could bind directly to the promoter of S100A14 and activate its transcription, which modulated the terminal differentiation in esophageal cancer (26,28).…”

The Fbw7 Tumor Suppressor Targets KLF5 for Ubiquitin-Mediated Degradation and Suppresses Breast Cell Proliferation

“…The KLF5 transcription factor has been shown to play important roles in cancer (14). Accumulated evidence suggests that KLF5 promotes fibroblast, colon, bladder, and breast cell proliferation (15)(16)(17).…”

Krüppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E2 Synthase 1 Gene Transcription in Breast Cancer

“…KLF5 (Krüppel-like factor 5)/IKLF/BTEB2 belongs to the human Sp1/KLF family of transcription factors containing three conserved C 2 H 2 -type zinc fingers in the C-terminal domain (1) and is highly expressed in estrogen receptor ␣ (ER␣) 2 -negative breast cancers (2). KLF5 promotes breast cell proliferation, survival, and tumorigenesis, partially by inducing FGF-BP1 (FGF-binding protein 1) gene expression (3), activating ERK signaling, and stabilizing the MKP-1 phosphatase (4).…”