KLF4 was first isolated by Shields et al. in 1996 from a NIH3T3 cDNA library . The gene is conserved among vertebrate species, from zebrafish to humans . Since its discovery, KLF4 has gained significant attention, particularly after it was identified in 2006 as one of the four key factors required for the induction of pluripotent stem cells (iPSCs) .
KLF4 contains three C2H2-type zinc fingers at the carboxyl terminus, which preferentially bind to GC-rich cis-DNA elements . This structure allows KLF4 to function as both an activator and repressor of gene expression . KLF4 is predominantly expressed in terminally differentiated epithelial tissues, including the skin, lung, and gastrointestinal tract .
KLF4 is involved in various cellular processes:
KLF4 has been studied extensively for its role in various diseases, including cancer. It has been shown to have different mechanisms in different tumors, but its prognostic role remains unclear . Despite the rapid progression in cancer research, the expression of KLF4 has not been consistently associated with prognosis for overall survival, disease-free survival, or disease-specific survival .