A novel high-content imaging-based technique for measuring binding of Dickkopf-1 to low-density lipoprotein receptor-related protein 6

Crystallographic mining of ASK1 regulators to unravel the intricate PPI interfaces for the discovery of small molecule

“…Dickkopf-3 (DKK3) is a secreted glycoprotein belonging to the members of the DKK family [116] , and has been broadly examined in the context of cancer, including liver cancer [19] . DKK1, 2, and 4 antagonize Wnt signaling when bound with Wnt co-receptor Lrp5/6 and Kremen proteins [117] , [118] , [119] , [120] , [121] . In contrast to other DKK family members, DKK3 is not able to bind Lrp and Kremen proteins [117] , [118] , [119] , [120] , [121] , [122] and its receptor remains to be explored [19] , [123] .…”

“…DKK1, 2, and 4 antagonize Wnt signaling when bound with Wnt co-receptor Lrp5/6 and Kremen proteins [117] , [118] , [119] , [120] , [121] . In contrast to other DKK family members, DKK3 is not able to bind Lrp and Kremen proteins [117] , [118] , [119] , [120] , [121] , [122] and its receptor remains to be explored [19] , [123] . Although, the function of DKK3 in the Wnt signaling pathway, as well as hepatic steatosis and associated metabolic disorders, has also been undetermined.…”

“…DKK3 level is increased in the blood of the aged population. Its expression is increased in prostate basal epithelial cells during cellular senescence [119] , suggesting that DKK3 might play a role in ageing-related disorders. An experimental examination reported that Dickkopf-3 (DKK3) expression was remarkably reduced in the liver of NAFLD patients, HFD or genetically induced obese mice, and palmitate stimulated cultured hepatocytes [19] .…”

Dickkopf Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role

“…Another DKK inhibitor is the small molecule NCI8642 (also named IIIC3 or Gallocyanin) which is able to block the interaction between DKK-1 [ 90 , 101 ] and DKK-2 [ 102 ] with LRP6 ( Figure 2 C). Despite the confirmed ability of this compound to inhibit DKK-1-LRP6 interaction and the reported therapeutic potential of the drug in Alzheimer’s disease [ 103 ], studies in human cancer are lacking.…”

Morphological profiling of human T and NK lymphocytes by high-content cell imaging

“…HCI is particularly suitable for systematic analysis of cellular phenotypes. It is employed widely in cancer and toxicology research on adherent cell lines to evaluate cellular fitness and viability upon drug treatment or genetic alterations (de Groot et al, 2018;Joshi and Lee, 2015;Papakonstantinou and O'Brien, 2014;Priestley et al, 2019;Wu and Li, 2018). HCI is also a powerful approach for identification of novel systemic properties of cells (Bryce et al, 2019;Caldera et al, 2019;Heigwer et al, 2018;Mattiazzi Usaj et al, 2020).…”