KLF4, p21 and context-dependent opposing forces in cancer

Abstract

| Krüppel-like factors are transcriptional regulators that influence several cellular functions, including proliferation. Recent studies have shown that one family member, KLF4, can function both as a tumour suppressor and an oncogene. The ability of KLF4 to affect the levels of expression of the cell-cycle regulator p21 seems to be involved, in that this protein might function as a switch that determines the outcome of KLF4 signalling. Is this role of p21 restricted to KLF4, or does p21 represent a nodal point for signals from multiple other factors with opposing functions in cancer?

Krüppel-like factor 4 exhibits antiapoptotic activity following γ-radiation-induced DNA damage

“…KLF4 has a dual function -to synergistically induce the expression of p21 WAF1/CIP1 with p53, leading to cell cycle arrest (Zhang et al, 2000) and to suppress BAX expression, both directly and indirectly by inhibiting activation of BAX by p53, thus reducing apoptosis (this study). This model may explain the context-dependent nature by which KLF4 functions as either a tumor suppressor or an oncogene as reported by various groups (Foster et al, 1999(Foster et al, , 2005Zhao et al, 2004;Rowland et al, 2005;Wei et al, 2005;Rowland and Peeper, 2006). It may also explain the recent finding that inactivation of p21 WAF1/CIP1 by oncogenic RAS V12 neutralizes the cytostatic action of KLF4, converting the latter to a transforming protein owing to its antiapoptotic activity (Rowland et al, 2005) Materials and methods…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…Krüppel-like factor 4 (KLF4), a zinc-finger containing transcription factor, regulates many cellular processes including cell proliferation, differentiation, apoptosis, and maintenance of tissue homeostasis [241]. Recent studies have demonstrated that KLF4 is one of four critical transcriptional factors (Oct3/4, Sox2, KLF4, and c-Myc) that orchestrate the reprogramming of differentiated cells into pluripotent stem cells [242].…”

“…Recent studies have demonstrated that KLF4 is one of four critical transcriptional factors (Oct3/4, Sox2, KLF4, and c-Myc) that orchestrate the reprogramming of differentiated cells into pluripotent stem cells [242]. Current studies in carcinogen-esis have revealed that KLF4 can function as both tumor promoter and tumor suppressor depending on tissue type and cellular context [241]. The oncogenic effect of KLF4 has been reported in breast and squamous cell carcinoma [243][244][245][246][247], while its tumor suppression role was reported in various types of cancers such as colon cancer [248,249].…”

Embryonic stem cell markers expression in cancers

“…Klf4 is an anti-proliferative factor in differentiated epithelia, and acts as a tumor suppressor in gastrointestinal cancers [24; 25]. However, Klf4 might also act as an oncogene [26]. It is overexpressed in laryngeal squamous cell carcinoma as an early event in its progression [27].…”