www.sciedu.ca/jst Journal of Solid Tumors, 2015, Vol. 5, No. 1 Published by Sciedu Press 49 REVI EW S KLF4 Genome: A double edged sword Deepti Malik, Deepak Kaul Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Correspondence: Deepak Kaul. Address: Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. Email: dkaul_24@hotmail.com Received: December 30, 2014 Accepted: January 27, 2015 Online Published: March 26, 2015 DOI : 10.5430/jst.v5n1p49 URL: http://dx.doi.org/10.5430/jst.v5n1p49 Abstract Kruppel like factor 4 (KLF4), member of SP1/KLF transcription factor family is characterized by three extremely conserved C2H2-type zinc-finger motifs at its carboxyl boundary that are crucial for its interaction with target DNA. Participation of KLF4 in the control of proliferation, differentiation and apoptosis are suggestive for KLF4 critical role in tumorigenesis. Depending on the genetic and cellular context, KLF4 gene acts as both oncogene and tumor-suppressor. KLF4 is a significant regulator in reprogramming of somatic cells to pluripotent cells that can give rise to all of the cell types that make up the body. Multiple in vitro and in vivo studies have shown inhibitory role of KLF4 in epithelial- mesenchymal transition (EMT) in various cancer types and loss of KLF4 expression during EMT significantly correlates with tumor angiogenesis, metastasis and aggressiveness. The manuscript updates the interrelationship that exists between epigenomic regulation of KLF4, its effector genes and oncogenic transformation. Key words Tumorigenesis, Genome, Kruppel like factor 4, Oncogene 1 KLF Genome: Evolution and nature Given the pivotal role played by Kruppel like factors (KLFs) in abroad spectrum of physiological and pathological processes, it is not surprising that these transcription factors have acquired great recognition all across the globe. Recent evidence have shown the involvement of KLFs in various processes including cell proliferation, differentiation, apoptosis, metabolism, inflammation, embryogenesis and tumorigenesis. Somatic cells can be re-programmed into pluripotent stem (iPS) and maintenance of embryonic stem cells pluripotent state is reliant on KLFs [1] . The three highly conserved cysteine and histidine (C2H2)-type zinc finger motifs at the carboxyl-terminus in KLF chain member’s exhibits shared ancestry to the Drosophila melanogaster Kruppel protein, accounting for the name. Although C-terminal region shares similarity, the amino-terminal region of KLFs family members vary significantly that allows them to bind to different coactivators, corepressors and modifiers [2] . Till now 17 members have been identified in Kruppel like factor family which are named from KLF1 to KLF17 [3] (see Figure 1). In recent time researchers have discovered a new variant of KLF gene/pseudogene christened as KLF18 which is widely suspected to be present in maximum number of placental mammals with sequenced genomes. KLF18 is chromosomally similar to KLF17 and is suspected to be a result of its duplication [4] . The KLF family members are divided into 3 clusters on the basis of functional characteristics. Cluster 1 comprises of KLFs 3, 8 and 12; Cluster 2 family members include KLFs 1,2,4,5,6 and 7 and Cluster 3 includes KLFs 9,10,11,13,14 and 16. Cluster 2 KLF