Intestinal Wnt in the transition from physiology to oncology

Table 1 Selection of assumed target genes of β-catenin

Gene	Function of the protein	Ref.
ATOH1	Transcription factor, secretory cell line differentiation	[137,138]
AXIN2	Part of destruction complex Wnt signaling	[139]
BCL2	Antiapoptotic	[140]
BIRC5	Apoptosis inhibitor	[141]
BMP4	Possible Wnt inhibitor	[142]
CCND1	Cell proliferation	[143]
CDKN2A	Cell cycle inhibitor	[144]
CDX1	Transcription factor, intestinal cell differentiation	[145]
CDX2	Transcription factor, intestinal cell differentiation	[146]
DKK1/4	Inhibitor of Wnt signaling	[147,148]
EPHB2/3	Migration and proliferation in intestine epithelial	[149]
HD5/6	Defensine, microbial defense	[150]
HEF1	Supports activation of oncogenic signaling pathways	[151]
HES1	Regulation of Notch signaling	[152]
JAG1	Ligand of Notch signaling	[153]
JUN	Cell cycle progression, apoptosis inhibitor	[154,155]
LGR5	Part of Wnt signaling	[156]
MDR1	Plasma membrane protein involved in the drug resistance	[123,124]
MET	Differentiation of intestinal epithelium	[157]
MYC	Protooncogene	[158]
MYCBP	Control of transcriptional activity of c-MYC	[159]
NOTCH2	Notch receptor	[160]
SGK1	Inhibits pro-apoptotic transcription factors	[161]
SOX9	Paneth cell differentiation	[32,162]
YAP	Transcription factor (Hippo signaling) activates genes involved in cell proliferation, suppresses apoptotic genes	[163]

ATOH1: Atonal BHLH transcription factor 1; BCL2: B-cell lymphoma 2 ; BIRC5: Baculoviral IAP repeat containing 5; BMP4: Bone morphogenetic protein 4; CCND1: Cyclin D1; CDKN2A: Cyclin dependent kinase inhibitor 2A; CDX1: Caudal type homeobox 1; CDX2: Caudal type homeobox 2; DKK: Dickkopf; EPHB2/3: EPH receptor B2/3; HD5/6: Human alpha defensin 5/6; HEF1: Human enhancer of filamentation 1; HES1: Hairy and enhancer of split-1; JAG1: Jagged Canonical Notch Ligand 1; JUN: C-Jun N-terminal kinase; LGR5: Leucine-rich repeat-containing G-protein coupled receptor 5; MDR1: Multidrug-Resistance-1; MET: Tyrosine-protein kinase Met; MYC: Myc proto-oncogene, bHLH transcription factor; MYCBP: MYC binding protein; NOTCH2: Notch Receptor 2; SGK1: Serum/glucocorticoid regulated kinase 1; SOX9: SRY-Box transcription factor 9; YAP: Yes-associated protein.

Table 2 Selection of potential target opportunities to inhibit Wnt/β-catenin signaling

Target	Effect	Ref.
Ligand-dependent Wnt signaling activation
Wnt ligands	Wnt inhibitors	[164]
	Posttranslational modification	[165]
Dkk1	Stabilization, increase of Dkk1	[128,166]
Transmembrane complex	Inhibition of Lgr5/6	[167]
	Inhibition of Frizzled	[168,169]
Dishevelled	Inhibition	[170]
Ligand independent Wnt signaling activation
Destruction complex	Stabilization of the destruction complex	[171,172]
β-catenin	Increase of degradation	[130,131]
	Inhibition of translocation to the nucleolus	[173]
β-catenin cofactors		[174]
Ribosome biogenesis		[134]
Oncolytic viruses		[132,133]

Dkk1: Dickkopf 1.