ABSTRACT
KLF5, a Krüppel-like family transcription factor, plays a potential role in cell proliferation, differentiation, tissue homeostasis and tumorigenesis. KLF5 is abundantly expressed in embryonic smooth muscle cells and is down-regulated with vascular development, but re-induced in proliferative smooth muscles in response to vascular injury. Homologous deletion of KLF5 is lethal and mice die before E8.5. Heterozygous mice appear grossly normal; however, these mice show cardiac hypertrophy and diminished angiogenesis and arterial wall thickening. KLF5 is involved in the regulation of angiogenesis during tumorigenesis and cancer progression by targeting or remodeling tumor microenvironment. KLF5 activates many genes that can contribute to angiogenesis such as platelet-derived growth factor (PDGF) A/B, Egr-1, plasminogen activator inhibitor-1 (PAI-1), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor receptors (VEGFR). KLF5 is regulated by many transcriptional regulators and nuclear receptors such as retinoic acid receptor-alpha (RARa), NF-kB, peroxisome proliferator-activated receptors (PPARg) and adenovirus E1A-associated cellular p300 transcriptional coactivator protein (p300). RARa antagonist activates KLF5 and induces angiogenesis.
KLF5 also plays an important role on the recruitment and activation of inflammatory cells that release cytokines and chemokines to induce hypoxia. This chapter will review recent studies carried out on the biological functions of KLF5 with an insight on the tumor angiogenesis.
