From: Wnt signaling in colorectal cancer: pathogenic role and therapeutic target
No. | Abbreviated name | Full official name | Classification | Intervention mechanism | References |
---|---|---|---|---|---|
1 | ACBP | Anticancer bioactive peptide | Novel bioactive peptide | ACBP can inhibit phospho-LRP6 and stimulate phospho-β-catenin. | [168] |
2 | ND | MiR-377-3p | MicroRNA | Directly target ZEB2 and XIAP to inhibit Wnt/β-catenin signaling | [169] |
3 | DHME | Dehydroxyhispolon methyl ether | Hispolon derivatives | Inhibits β-catenin-mediated T cell factor (TCF)-dependent transcriptional activity | [170] |
4 | ND | SSTC3 | New small molecule CK1α activator | The target CK1α inhibits the growth of mouse CRC xenografts and attenuates the growth of patient-derived metastatic CRC xenografts | [171] |
5 | CQD | Chlorquinaldol | Bacteriostatic agent | Inhibit the acetylation of β-catenin, destroy the interaction between β-catenin and T cell factor 4 (TCF4), and reduce the binding of β-catenin to Wnt target gene promoters, and down-regulate the expression of these target genes | [172] |
6 | ND | KY7749 | Compound | Inhibit the proliferation and transformation of CRC cells, independently of β-catenin degradation of Ras | [173] |
7 | ND | Niclosamide | Antihelminth compound | Inhibit Wnt/β-catenin pathway activation, down-regulate Dvl2, and reduce downstream β-catenin signal transduction | [174] |
8 | ND | KHDRBS3 | Genes encoding KH RNA binding domains, signal transduction related 3 | KHDRBS3 may play a key role in acquiring stem cell characteristics (such as drug resistance and spheroid/organoid formation) by regulating the expression of CD44 variants and the Wnt signaling pathway | [175] |
9 | ND | KYA1797K | Compound | GSK3β activates small molecules that degrade β-catenin and Ras, inhibits KRAS mutations, and reduces β-catenin, RAS and EGFR levels by targeting the Wnt/β-catenin pathway | [176] |
10 | ND | MiR-506 | MicroRNA | Inhibit MDR1/P-gp expression by down-regulating the Wnt/β-catenin pathway | [177] |
11 | ND | MiR-148a | MicroRNA | Suppresses the expression of WNT10b and β-catenin signaling, and suppresses the expression of stem cells. | [178] |
12 | MAGI1 | MAGUK with inverted domain structure-1 | Scaffold protein | Stabilize the location of E-cadherin and β-catenin at the cell-cell junction, enhance the formation of actin stress fibers and adhesion plaques, increase cell adhesion to matrix proteins and inhibit Wnt signaling, independent of adhesion Growth, in vitro migration and invasion | [179] |
13 | ND | BMP7v | Bone morphogenetic proteins | BMP7v treatment promotes CR-CSC differentiation and reproduces cell differentiation-related gene expression profiles by inhibiting Wnt pathway activity and reducing the mesenchymal characteristics and survival of CR-CSC | [180] |
14 | NSAID | Sulindac on nuclear | Nonsteroidal anti-inflammatory drugs | Eliminates β-catenin/TCF-mediated transcription in CRC cell lines DLD1 and SW480, and reduces the level of non-phosphorylated β-catenin | [181] |
15 | 4βHWE | 4β-Hydroxywithanolide E | Novel Antagonist of Wnt Signaling | Promote the phosphorylation and degradation of β-catenin, and subsequently inhibit its nuclear translocation, mediate G0/G1 cell cycle arrest and apoptosis, and weaken the Wnt/β-catenin signaling pathway | [182] |
16 | ND | HGC33-SFB-NP | HGC33 modified NPs | Inhibit Wnt-induced signal transduction, and inhibit G0/1 cells down-regulating the expression of cyclin D1, thereby inhibiting epithelial-mesenchymal transition | [183] |
17 | Si-WNT8b | Small interfering RNA against WNT8b | Small interfering RNA against WNT8b | Reduces the levels of WNT8b, frizzled-4, β-catenin, phosphorylated GSK-3β (p-GSK-3β) and cyclin-D, while it increases the levels of p-β-catenin and GSK-3β | [184] |
18 | ND | lncRNA DANCR | Long non-coding RNAs | Significantly reduces the expression levels of p-GSK-3β and β-catenin, and inhibits the activation of Wnt/β-catenin signaling pathway | [185] |
19 | plopP | Inorganic polyphosphate | Phosphate Compound | Mediates cyclin D1 expression and nuclear localization are IKKÉ‘ and ERK1/2 dependent | [186] |
20 | ND | AC007271.3 | Long noncoding RNA | Promote OSCC cell proliferation, invasion and inhibit cell apoptosis through Wnt/β-catenin signaling pathway | [187] |
21 | CORM2 | CO-releasing molecule 2 | Exogenous small molecules | Significantly reduce cell apoptosis, cytochrome release from mitochondria to cytoplasm, MPTP opening and caspase-3 cleavage, inhibition of superoxide anion generation in the response of HUVECs to ox-LDL and Wnt/β-catenin pathway activation | [188] |
22 | ND | VALD-3 | Schiff base compounds | Inhibition of Wnt/β-catenin signaling pathway induces apoptosis and cell cycle arrest in human cancer cells | [189] |
23 | CDK14 | Cyclin-dependent kinase 14 | Protein kinase | CDK14 inhibition mediated Wnt signaling pathway can inhibit cancer cell proliferation, invasion and migration | [190] |
24 | ND | FL118 | A novel camptothecin analogue | Significantly inhibits the expression of vimentin, and at the same time enhances the expression of E-cadherin. It is detected that the expression of β-catenin and its target survivin and cyclin D1 are reduced | [191] |
25 | ND | Prednisolone | Glucocorticoid | It is possible to inhibit Wnt signaling by inhibiting the co-receptor of the Wnt/β-catenin signaling pathway in the early stage of glucocorticoid therapy and inhibiting its ligand in the following weeks | [192] |
26 | ND | 3-Cl-AHPC | Adamantyl-substituted retinoid-related | Inhibit Wnt/β-catenin pathway, reduce β-catenin nuclear localization and inhibit Wnt/β-catenin activation of transcription factor TCF/LEF | [193] |
27 | ND | MiR-603 | MicroRNA | Overexpression promotes nuclear β-catenin levels and TOPflash luciferase activity, and activates the Wnt/β-catenin signaling pathway | [194] |
28 | ND | IWP-2 | A Wnt signal inhibitor | Improve neuropathic pain by inhibiting Wnt/β-catenin pathway | [195] |
29 | ND | RBM5 | RNA binding motif protein | By inhibiting Wnt/β-catenin signal transduction and inducing cell apoptosis | [196] |
30 | ND | MiR-384 | MicroRNA | Targets Smad5 and inactivates the Wnt/β-catenin pathway | [197] |
31 | ND | b-AP15 | Inhibitor of the ubiquitin-specific peptidase 14 | Increase endoplasmic reticulum stress/UPR and inhibit Wnt/Notch1 signaling pathway | [198] |
32 | ND | MiR-20b | MicroRNA | May inhibit APC through canonical Wnt signaling pathway | [199] |
33 | ND | Hsa_circ_0004018 | Circular RNA | Targeting miR-626/ inhibits Wnt/β-catenin signaling pathway, blocking the growth of xenograft tumors in vivo | [200] |
34 | ND | Lanatoside C | Cardiac glycosides | Blocking the MAPK/Wnt/PAM signaling pathway prevents the G2/M phase of the cell cycle from exerting its anti-cancer activity | [201] |
35 | ND | MiR-216a | MicroRNA | Demethylated miR-216a down-regulates HMGB3 and inhibits cell proliferation, migration and invasion. Inhibition of HMGB3 expression can induce apoptosis, inhibit cell proliferation, and down-regulate Wnt/β-catenin pathway activity. | [202] |
36 | ND | MiR-375-3p | MicroRNA | Directly inhibit the expression of FZD8 to block the Wnt/β-catenin pathway and downstream molecules Cyclin D1 and c-Myc, which can increase the expression of caspase 1 and caspase 3, and promote T24 cell apoptosis | [203] |
37 | ND | TIPE1 | TNFAIP8 | Significantly inhibits the expression and activity of MMP2 and MMP9, and mediates Wnt/β-catenin signaling | [204] |
38 | ANP | Atrial natriuretic peptide | Small peptide | Triggers NHE-1 mediated increase in intracellular acidity, through Frizzled-mediated activation, which acts on the upstream of the cascade, while EIPA acts on the downstream to inhibit Wnt/ β-catenin signaling | [205] |
39 | BI | Benzyl isothiocyanate | ND | Targeting undifferentiated CSC reduces the number of cells containing β-catenin in the nucleus | [206] |
40 | PI | Phenethylisothiocyanate | ND | Reduce the number of cells containing β-catenin in the nucleus, effectively inhibit the growth of multicellular tumor spheroid models that mimic micrometastasis | [206] |
41 | ND | MiR-624-5p | MicroRNA | Induce cell senescence, block the growth of experimental HBL, and directly target the 3′-untranslated region of β-catenin | [207] |
42 | ND | Z-Ajoene | ND | Promote the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner | [208] |
43 | TgROP18 | ROP18 from T. gondii | Toxoplasma | Specific binding of different host immune-related molecules to mediate the suppression of host innate and adaptive immune response | [209] |
44 | ND | RIG-3 | Cell surface Ig superfamily proteins | Inhibition of CAM-1, a Ror type receptor tyrosine kinase that binds to Wnt ligands, regulates Wnt signaling | [210] |
45 | ND | Pyrvinium | Small molecule | Increase the proliferation of MSC while inhibiting its osteogenic and chondrocyte lineages by reducing cytoplasmic β-catenin | [211] |
46 | ND | LiCl | Small molecule | Inhibition of GSK-3beta promotes canonical Wnt signaling, increases β-catenin nuclear translocation and upregulates the transcriptional activity of canonical Wnt-responsive promoters | [212] |
47 | TZDs | Thiazolidinediones | Small molecule | Down-regulate DNA synthesis in MDA-MB-231 and T47D, and reduce Wnt co-receptor frizzled-1 and low-density lipoprotein-related protein 6 (LRP6) mRNA expression and LRP6. Targeting downstream Wnt signaling molecules in T47D cells, down-regulating p-β-catenin (S33/S37/T41) and promoting β-catenin translocation into the nucleus | [213] |
48 | ND | MiR-376c | MicroRNA | Targeting Wnt-3, ARF-GEF-1 inhibits ARF-6 activation, thereby preventing the release of β-catenin and its transactivation, thereby inhibiting osteoblast differentiation | [214] |
49 | SKI II | SphK1 inhibitor II | Inhibitor | Mediates β-catenin degradation through Wnt5A | [215] |
50 | ND | MiR-376c | MicroRNA | Inhibit YTHDF1 expression and Wnt/β-catenin pathway induction | [216] |
51 | Li | Lithium | Small molecule | Significantly inhibits BMP-2’s stimulation of cartilage formation and GSK-3beta enzyme activity, and reduces the levels of N-cadherin and mRNA, and reduces the total level of LEF-1 and β-catenin by BMP-2 Up-regulation of nuclear levels reduces the interaction of β-catenin with GSK-3beta | [217] |
52 | ND | SP600125 | JNK inhibitor | Prevents Wnt5a-induced CXCR4 expression and cell migration in SFRP5-negative cells | [218] |
53 | ND | FH535 | Wnt signaling pathway inhibitor | Regulate the expression of CyclinA2 and Claudin1 genes to inhibit the proliferation and migration of colorectal cancer cells, and down-regulate β-catenin | [219] |
54 | CEACAM1 | Cell adhesion molecule 1 | Cell adhesion molecule | Site-specific regulation of β-catenin phosphorylation to control EMT | [220] |
55 | PBN | Probenecid | Small molecule | Blocking the PANX1 channel reduces the release of ATP in A375-P cells and reduces β-catenin levels | [221] |
56 | CPX | Ciclopirox | Small molecule | Inhibit cell proliferation, induce cell apoptosis, inhibit cell migration and invasion, inhibit angiogenesis and lymphangiogenesis to exert its anti-cancer activity, and mediate Wnt/β-catenin signal transduction | [222] |
57 | ND | Anti-IL-3R-EVs | Inhibitor | MiR-214-3p, which directly targets β-catenin, was upregulated, while miR-24-3p, which targets adenomatous polyposis (APC) and glycogen synthase kinase-3β (GSK3β), was found to be downregulated | [223] |
58 | ND | E-cadherin | Cadherin | Inhibit the cell surface localization of endogenous M-cadherin and N-cadherin, as well as cell-cell fusion, dominant negative β-catenin mutant, and inhibit Wnt/β-catenin signaling | [224] |
59 | W9 | WP9QY | Peptides | Inhibition of Wnt/β-catenin signaling inhibits osteoclast production and enhances osteoblast production by reducing the expression of sclerostin in alveolar bone | [225] |
60 | ND | Collagen XVIII | Collagen | The long isoform contains a coiled (Fz) domain with Wnt inhibitory activity, which can inhibit the migration and proliferation of endothelial cells or induce their death to effectively reduce tumor angiogenesis and growth | [226] |
61 | ND | lncRNA BCYRN1 | lncRNA | Inhibit Wnt/−catenin pathway to inhibit cell proliferation and migration and induce apoptosis | [227] |
62 | Box 5 | N-butyloxycarbonyl hexapeptide | Peptides | Directly inhibit Wnt5a-induced protein kinase C and Ca(2+) signals | [228] |
63 | ND | Receptor tyrosine kinase Ror2 | Kinase | Activating the Wnt-JNK pathway and inhibiting the β-catenin-TCF pathway play an important role in mediating non-canonical Wnt5a signaling | [229] |
64 | ND | Phosphoprotein phosphatase-2A | Phosphatase | Inhibit Wnt3a | [230] |
65 | MIR155 HG | MIR155 host gene | Long noncoding RNA | Inhibit the production of its derivatives miR-155-5p and miR-155-3p, and reduce the small interfering RNA. MIR155HG can inhibit cell proliferation, migration, invasion and in situ glioma growth, and target the inhibition of Wnt/β-catenin pathway | [231] |
66 | ND | XAV939 | A small inhibiter | Inhibition of tankyrase and subsequent stabilization of cytoplasmic axin levels strongly inhibits the Wnt pathway | [232] |
67 | TSK | Tsukushi | Small leucine-rich proteoglycan family | inhibits signaling molecules, such as BMP and Wnt | [233] |
68 | ND | HDAC-inhibitor | Inhibitor | Decreases the number/activity of β-catenin transcription factor, which promotes cell growth arrest by reducing the expression of c-Myc and cyclin D1 and eliminating the pro-survival Wnt/β-catenin signaling pathway | [234] |