WIF1 can effectively co-regulate pro-apoptotic activity through the combination with DKK1

Dickkopf-3 (DKK-3) obstructs VEGFR-2/Akt/mTOR signaling cascade by interacting of β2-microglobulin (β2M) in ovarian tumorigenesis

“…mTORC1 integrates cellular signals derived from energy, nutrients and growth factors in order to regulate the functional activity and phosphorylation of two major down-stream substrates, which are included in protein translation, namely S6K and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). In addition, HIF-1α and its down-stream target molecule, VEGF, play an essential role in tumor angiogenesis [52,[82][83][84]. Our data observed that DKK-3-induced PI3K and Akt de-phosphorylation were significantly restored by β2M.…”

“…Wnt signaling is initially stimulated by the protein interaction of a Wnt-protein ligand to a Frizzled (Fz) family receptor [49]. Subsequently, disheveled (Dvl) is then phosphorylated, which inhibits glycogen synthase kinase (GSK)-3β activity through its cellular communication with the axis inhibition protein (Axin) [50][51][52]. On the other hand, human diseases related with mutations of the Wnt signaling cascade components including mutations in various Wnt ligands, antagonists, and agonists-associated gene.…”

Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway

“…Melatonin may decrease DKK1 via downregulation of p53. DKK1 is induced by p53 because the Dkk1 transcription start site has a p53 responsive element (Caricasole et al, 2004[9]; Wang et al, 2000[58]), whereas DKK1 and Wnt inhibitory factor-1 (WIF1) significantly activated the transcription of p53 in ovarian carcinoma cells (Ko et al, 2014[30]). In addition, mature neurons exposed to DKK1 showed a decrease in the number of functional synaptic vesicle recycling sites, and DKK1 promoted the dispersion of pre- and postsynaptic proteins, indicating a loss of synapses (Purro et al, 2014[46]).…”

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

“…In addition, another study suggests that WIF-1 may inhibit angiogenesis. DKK-1 and WIF-1 directly interact and together may act as co-regulators in promoting apoptosis in the human umbilical vein endothelial cell (HUVEC) system (Ko et al, 2014). …”