2021
DOI: 10.3390/cancers13205135
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KLF4 Induces Mesenchymal–Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors

Abstract: Epithelial–Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription factors acting in concert. While EMT-inducing transcription factors (TFs)—TWIST1/2, ZEB1/2, SNAIL1/2/3, GSC, and FOXC2—are well-characterized, the MET-inducing TFs are relatively poorly understood (OVOL1/2 and GRHL1/2). Here, using mechanism-based mathematica… Show more

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Cited by 29 publications
(25 citation statements)
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“…Krüppel-like factors (KLFs) are part of the zinc-finger family of TFs and are closely related to the SP family and regulate several critical development processes by activating/repressing many genes [ 58 , 59 ]. KLF4 regulates cell proliferation, differentiation, and adipogenesis [ 58 , 60 , 61 ]. KLF10 is induced by TGFβ and is implicated in cell differentiation, apoptosis, osteoblast and osteoclast differentiation, gluconeogenesis, and inflammation [ 62 , 63 , 64 , 65 ].…”
Section: Discussionmentioning
confidence: 99%
“…Krüppel-like factors (KLFs) are part of the zinc-finger family of TFs and are closely related to the SP family and regulate several critical development processes by activating/repressing many genes [ 58 , 59 ]. KLF4 regulates cell proliferation, differentiation, and adipogenesis [ 58 , 60 , 61 ]. KLF10 is induced by TGFβ and is implicated in cell differentiation, apoptosis, osteoblast and osteoclast differentiation, gluconeogenesis, and inflammation [ 62 , 63 , 64 , 65 ].…”
Section: Discussionmentioning
confidence: 99%
“…For instance, ZEB2 is considered an inducer of EMT in epithelial cancers, but in the context of melanoma, it inhibits the mesenchymal phenotype ( 19 , 50 ). Other molecules that show opposite effects include KLF4 ( 51 , 52 ) and TFAP2A ( 53 , 54 ). Thus, understanding the mechanistic underpinning of how the de-differentiation and EMT programs are linked can help decipher reasons for the similarities and differences between these pathways across cancers.…”
Section: Introductionmentioning
confidence: 99%
“…Next, we examined the role of ELF3 in modulating EMT dynamics. We analyzed the interaction dynamics between ELF3 and a core EMT regulatory circuit (denoted by black dotted rectangle in Fig 2E ) comprised of five core factors: three EMT-inducing transcription factors (EMT-TFs) - ZEB1/2, SNAIL, and SLUG - and two EMT-inhibiting factors: the microRNA miR-200 family (Gregory et al ., 2008) and KLF4, a transcription factor that correlates with the epithelial phenotype (Yori et al ., 2010; Subbalakshmi et al ., 2021). First, we plotted a bifurcation diagram to track the levels of ZEB1/2 mRNA (as a readout of EMT phenotype) in response to an external EMT-inducing signal I_ext ( Fig 2F ).…”
Section: Resultsmentioning
confidence: 99%