Dickkopfs and Wnt/β-catenin signalling in liver cancer

Table 1 Downstream molecules of the Wnt/β-catenin pathway with overexpression in hepatocellular carcinoma

Gene	Ref.
c-Myc	[159]
Cyclin D1	[57]
Dickkopf 1	[126]
Epidermal growth factor receptor	[51]
Glutamine synthetase	[63]
Glutamate transporter	[63]
Leukocyte cell-derived chemotaxin 2	[160]
Ornithine aminotransferase	[63]
Orphan G-protein-coupled receptor	[64]
Regenerating islet-derived 1 α	[161]
Regenerating islet-derived 3 α	[161]

Table 2 Aberrant expression of Wnt/β-catenin pathway components in liver cancer

Component	Expression in tumour tissues vs non-tumour/healthy tissues	Incidence (%)	Method	Ref.
β-catenin	High	40-70	IHC	[40-43]
Wnt1	High	41	PCR	[69]
Wnt3	High	39-76	PCR	[70,71]
Wnt4	High	20	PCR	[71]
Wnt5A	High	25	PCR	[71]
FZD3	High	41	PCR	[71]
FZD6	High	31	PCR	[71]
FZD7	High	33-90	PCR	[70-72]
phospho-GSK3β	High	52	IHC	[73]
Axin1	Low	67	IHC	[76]
Dvl	High	71	Western blotting	[82]
Prickle-1	Low	55	PCR	[82]
HDPR1	Low	58	PCR	[83]
PIN1	High	53	Western blotting	[65]
TCF-4	High	91	PCR	[87]
LEF-1	High	52	IHC	[88]
CDH17	High	72	IHC	[90]

CDH17: Cadherin-17; Dvl: Dishevelled; FZD: Frizzled; phospho-GSK3β: Phosphorylated glycogen synthase kinase 3β; HDPR1: Human homologue of Dapper; IHC: Immunohistochemistry; LEF: Lymphoid enhancer factor; PCR: Polymerase chain reaction; PIN1: Peptidyl-prolyl cis/trans isomerase; TCF: T-cell factor.

Table 3 Differences between the DKK family members

Property	DKK1	DKK2	DKK3	DKK4	Ref.
Variants	Unknown	Unknown	2	Unknown	[130]
Location of Cys-1	85-138 amino acids	78-127 amino acids	147-195 amino acids	41-90 amino acids	[110]
Location of Cys-2	189-263 amino acids	183-256 amino acids	208-284 amino acids	145-218 amino acids	[110]
Length of linker region (number of amino acids)	50	56	12	54	[110]
Receptor	LRP5/LRP6	LRP5/LRP6	Not identified	LRP5/LRP6	[113]
Activity in Wnt/β-catenin signalling in HCC	Antagonist	Not reported	Not reported	Not reported	[126]
Expression in HCC tissues	Overexpressed	Reduced	Reduced	Not reported	[126,143]
Phenotype of knockout mice	Embryonic lethality	Viable, fertile, blindness, osteopaenia	Viable, fertile, hyperactive, increased IgM, natural killer cells and haematocrit levels	Not reported	[116,162-164]

Cys-1: Amino-terminal cysteine-rich domain; Cys-2: Carboxyl-terminal cysteine-rich domain; HCC: Hepatocellular carcinoma; LRP: Lipoprotein receptor-related protein; DKK: Dickkopf.