Table 2.

Preclinical evidence for DKK1 promoting cancer pathogenesis

Cancer	Selected evidence for DKK1 cancer‐promoting activity	Reference
Breast	DKK1 increased tumour growth and neovascularization in a xenograft model Cancer cells with metastatic potential avoided immune clearance by expressing DKK1	(Voorzanger‐Rousselot et al., 2007; Smadja et al., 2010; Malladi et al., 2016)
Cholangiocarcinoma	DKK1 knockdown decreased migration, invasion, proliferation, tumour growth and expression of VEGF‐C and MMP9	(Shi et al., 2013; Shi et al., 2016)
Colorectal	DKK1 regulated the expression of cancer‐related genes	(Aguilera et al., 2015)
Oesophageal	Overexpression of DKK1 increased proliferation and invasion	(Li et al., 2011)
Liver	DKK1 promoted migration, invasion, tumour growth, metastasis and angiogenesis Cancer stem cell‐like liver cells had increased expression of DKK1	(Yu et al., 2009; Tung et al., 2011; Chen et al., 2013; Tao et al., 2013; Huang et al., 2014; Kim et al., 2015; Chen et al., 2016)
Laryngeal	DKK1 knockdown reduced migration, invasion and proliferation	(Shi et al., 2014)
Lung	An anti‐DKK1 antibody had efficacy in a syngeneic mouse model Cancer cells with metastatic potential avoided immune clearance by expressing DKK1 An anti‐DKK1 antibody induced apoptosis, reduced invasion, decreased proliferation and had efficacy in a xenograft model DKK1 overexpression promoted invasion, migration and proliferation DKK1 activated PI3K/Akt signalling through a novel receptor (CKAP4)	(Sato et al., 2010; Li et al., 2013; Salim et al., 2015; D'Amico et al., 2016; Kimura et al., 2016; Malladi et al., 2016; Yao et al., 2016; Pang et al., 2017)
Melanoma	An anti‐DKK1 antibody had efficacy in a syngeneic mouse model	(D'Amico et al., 2016)
MFH	DKK1 promoted transformation of hMSCs to MFH cells	(Matushansky et al., 2007)
Multiple myeloma	Anti‐DKK1 antibodies had efficacy in mouse models Anti‐DKK1 antibodies improved bone health in mouse models	(Yaccoby et al., 2007; Fulciniti et al., 2009; Heath et al., 2009; Pozzi et al., 2013)
Osteosarcoma	An anti‐DKK1 antibody had efficacy in PDX models DKK1 overexpression increased proliferation and tumour growth	(Gregory et al., 2003; Krause et al., 2014; Goldstein et al., 2016)
Ovarian	DKK1 knockdown had efficacy in a xenograft model	(Wang and Zhang, 2011)
Pancreatic	DKK1 knockdown decreased migration, invasion and proliferation DKK1 activated PI3K/Akt signalling through a novel receptor (CKAP4)	(Takahashi et al., 2010; Kimura et al., 2016)
Prostate	DKK1 overexpression increased tumour growth and metastasis An anti‐DKK1 antibody reduced tumour growth in a xenograft model	(Hall et al., 2010; Thudi et al., 2011)

MFH, malignant fibrous histiocytoma; hMSCs, human mesenchymal stem cells; PDX, patient‐derived xenograft.