KLF4 signalling in carcinogenesis and epigenetic regulation of hTERT

Gene expression is crucial and tightly regulated to steer the development, differentiation, proliferation and even apoptosis of a cell. Each cell and tissue type shows a unique repertoire of transcription factors. Tissue micro-environmental regulation of epigenetic signature of a gene has been documented in many cases. Epigenetic factors play a significant role in the regulation of gene expression. KLF4 is a well-known transcription factor regulating the expression of several genes including hTERT. KLF4 functions both as a tumor suppressor and oncogene depending on cell type. hTERT, upregulated in the majority of cancers as against its undetectable expression in differentiated cells, is one of the target genes for KLF4. Here we hypothesize that KLF4 differentially regulates epigenetic modification of the promoter of hTERT and consequently its expression in different tissue microenvironments. The proposed hypothesis explains the dual role of KLF4 in two different tissue microenvironments with respect to the regulation of hTERT expression. Since both KLF4 and hTERT are key molecules to maintain the stemness and immortality of cancer cells, defining the crosstalk between these two molecules may open new avenues for cancer therapeutics. Also, exploring the proposed hypothesis may unravel the cause of ambiguous nature of KLF4 in carcinogenesis.