The transcription factor Kruppel-like factor 4 (KLF4) directly actives transcription of the CDH1 by binding to the GC-rich/E-box region of the CDH1 gene promoter (Yori et al. 2010; Koopmansch et al. 2013). KLF4 is an important regulator of proliferation and differentiation of epithelial cells during development and tumorigenesis, thought to play a tumor suppressor role. KLF4-mediated upregulation of CDH1 levels suppresses migration and invasiveness of tumor cells of epithelial origin (Yori et al. 2010). KLF4-mediated activation of the CDH1 gene transcription may be facilitated by the formation of a complex between KLF4 and transcription factors PBX1 and MEIS2 at the CDH1 gene promoter (Bjerke et al. 2011) or by a cooperative action of KLF4 and the homeobox protein MSX2 at the CDH1 gene promoter (Lin et al. 2018). Direct upregulation of CDH1 by KLF4 is evolutionarily conserved in mouse, where it occurs downstream of the nuclear factor I-C (NFIC) during dentogenesis (Lee et al. 2014). Depending on the cellular context, KLF4 binding to the CDH1 gene promoter may have a repressive effect on the CDH1 gene transcription (Lai et al. 2012).