The Role of Cadherin 17 (CDH17) in Cancer Progression via Wnt/β-Catenin Signalling Pathway: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Information Source and Search Strategy
2.3. Inclusion and Exclusion Criteria
2.4. Study Selection
2.5. Data Extraction and Analysis
2.6. Sensitivity Analysis
2.7. Quality Assessment
2.8. Effect Measures
2.9. Certainty of Evidence
3. Results
3.1. Search Results
3.2. Study Characteristics
3.3. Quality and Risk of Bias Assessment
3.4. Certainity of Evidence
3.5. Narrative Synthesis
3.6. Meta-Analysis of Outcomes
3.6.1. CDH17 as a Pro-Tumorigenic Factor Driving Malignant Phenotypic Change
3.6.2. CDH17 as an Upstream Activator of the Wnt/β-Catenin Pathway
3.6.3. Sub-Group Analysis of Clinical Data Indicates Sex Dependent Role of CDH17 in Cancer Progression
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
APC | Adenomatous polyposis coli |
CK1α | Casein kinase 1α |
CRC | Colorectal cancer |
DVL | Dishevelled |
EMT | Epithelial–mesenchymal transition |
ERK | Extracellular signal-regulated kinase |
FAK | Focal adhesion kinase |
FZD | Wnt ligands bind frizzled |
GC | Gastric cancer |
GRADE | Grading of Recommendations Assessment, Development, and Evaluation |
GSK-3β | Glycogen synthase kinase 3β |
HCC | Hepatocellular carcinoma |
IHC | Immunohistochemistry |
IV | Inverse variance |
KD | Knockdown |
KO | Knockout |
LEF | Lymphoid enhancer-binding factor |
LGR | Leucine-rich repeat-containing G-protein-coupled receptor |
LRP5/6 | Low-density lipoprotein receptor-related proteins 5 and 6 |
MA | Meta-analysis |
MD | Mean difference |
NEC | Neuroendocrine tumours |
NOS | Newcastle–Ottawa Scale |
OHAT | Office of Health Assessment and Translation |
PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
PROSPERO | Prospective Register of Systematic Reviews |
Rb | Retinoblastoma |
RCTs | Non-randomised controlled trials |
RoB | Risk of bias |
SD | Standard deviation |
SEM | Standard error of mean |
shRNA | Short hairpin RNA |
siRNA | Small interfering RNA |
SMD | Standardised mean difference |
SR | Systematic review |
SYRCLE | Systematic Review Centre for Laboratory Animal Experimentation |
TAZ | Transcriptional co-activator with PDZ-binding motif |
TCF | T-cell factor |
TNM | Tumour-Node-Metastasis |
WB | Western blotting |
YAP | Yes-associated protein |
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Articles | Year | Cancer Type | Study Design | Models | Groups (Exposure vs. Control) | Outcome Measures |
---|---|---|---|---|---|---|
Bartolomé et al. [21] | 2025 | CRC | Preclinical study | In vitro (cell-line; KM12SM & SW620; n = 3) | CDH17-specific shRNA (sh60) vs. scrambled shRNA (control) | TOP/FOP reporter assay, gene expression |
Liu et al. [6] | 2009 | HCC | Preclinical study; cross-sectional | In vitro (cell-line; MHCC97H, n = NS) In vivo (athymic BALB/c nu/nu mice; n = 3, n = 5), Clinical (n = 46) | CDH17-specific constructs and shRNA vs. empty vector | TOP/FOP assay, WB |
Wang et al. [30] | 2013 | HCC | Preclinical study | In vitro (cell-line; MHCC97L, MHCC97H n = 3), in vivo (BALB/c ByJ mice; n = 6) | Lic5 antibody-treated (CDH17-suppressed) MHCC97L cells vs. PBS-treated MHCC97L cells | WB, qPCR, IHC |
Qiu et al. [20] | 2019 | GC | Preclinical study; cross-sectional | In vitro (AGS & MKN-45, n = 3), In vivo (nude mice; n = 5), Clinical (n = 156) | CDH17 shRNA vector/CDH17 lentiviral shRNAmir vs. mock control) | TOP/FOP assay, WB |
Qu et al. [22] | 2017 | GC | Preclinical study | In vitro (AGS & SGC-7901 cells, n = 3) | CDH17 lentiviral shRNA (sc-43014-V) vs. empty vector | WB |
References | Title | Comparison Detail | Comparison Outcome |
---|---|---|---|
[21] | Loss of cadherin 17 downregulates LGR5 expression, stem cell properties and drug resistance in metastatic colorectal cancer cells | Global transcriptomic analysis was performed to compare shRNA (KD) of KM12SM and SW620 cells with the scramble control (SCR) to identify affected genes and signalling pathways. Wnt/β-catenin signalling activity was assessed using TOP/FOP reporter assays and Western blot. | CDH17 KD group > control group (GSK3B expression, AXIN expression, CSNK1A expression, DKK4 and DKK1) CDH17 KD group < control group (responsiveness to Wnt3a in TOP/FOP assays) |
[6] | Targeting cadherin-17 inactivates Wnt signalling and inhibits tumour growth in liver carcinoma | A TOP/FOP Flash luciferase assay was performed in MHCC97H cells with or without CDH17 shRNA transfection (Vector and Mock controls). Western blotting was used to examine Wnt pathway proteins. In vivo, immunohistochemistry was carried out for tumour tissues from both treated and control groups. | CDH17 KD group < control group (total β-catenin levels, cyclin D1 levels, phospho-GSK-3β levels, TOP/FOP luciferase activity) CDH17 KD > Vector/Mock controls (Rb expression) |
[30] | Anti-cadherin-17 antibody modulates beta-catenin signalling and tumorigenicity of hepatocellular carcinoma | AGS & SGC-7901 cells treated with anti-CDH17 antibody were analysed by immunofluorescence to assess total and phosphorylated β-catenin levels. Real-time qPCR was used to measure cyclin D1 gene expression. In vivo, Wnt/β-catenin pathway targets were examined using Western blot and immunohistochemistry. | CDH17 inhibited group < control group (total β-catenin, phospho-β-catenin [Thr41/Ser45], cyclin D1 expression) Lic5-treated group > control group (Rb expression) |
[20] | Targeting CDH17 Suppresses Tumour Progression in Gastric Cancer by Downregulating Wnt/beta-Catenin Signalling | A TOP flash/FOP flash reporter assay was conducted in AGS and MKN-45 cells following CDH17 silencing. To further validate the modulation of the Wnt/β-catenin pathway, Western blot analysis was used to assess the expression of key pathway components. | CDH17 KD group < control group (total and nuclear β-catenin, Phospho-GSK-3β, Cyclin D1, TCF/LEF transactivation activity) CDH17 KD group > control group (Rb, p53, p21 expression) |
[22] | CDH17 is a downstream effector of HOXA13 in modulating the Wnt/beta-catenin signalling pathway in gastric cancer | Western blot assay was used to assess β-catenin between the knock down group and the control group in SGC-7901 cells. | CDH17 KD group < control group (β-catenin expression) |
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Tha Shrestha, B.; Feng, Y.; Lad, A.; Bates, A.; Chen, J.; Brown, K.; Zeng, F.; Wang, N. The Role of Cadherin 17 (CDH17) in Cancer Progression via Wnt/β-Catenin Signalling Pathway: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2025, 26, 9838. https://doi.org/10.3390/ijms26209838
Tha Shrestha B, Feng Y, Lad A, Bates A, Chen J, Brown K, Zeng F, Wang N. The Role of Cadherin 17 (CDH17) in Cancer Progression via Wnt/β-Catenin Signalling Pathway: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2025; 26(20):9838. https://doi.org/10.3390/ijms26209838
Chicago/Turabian StyleTha Shrestha, Bipusha, Yahui Feng, Aaron Lad, Anthony Bates, Jing Chen, Karen Brown, Feier Zeng, and Ning Wang. 2025. "The Role of Cadherin 17 (CDH17) in Cancer Progression via Wnt/β-Catenin Signalling Pathway: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 26, no. 20: 9838. https://doi.org/10.3390/ijms26209838
APA StyleTha Shrestha, B., Feng, Y., Lad, A., Bates, A., Chen, J., Brown, K., Zeng, F., & Wang, N. (2025). The Role of Cadherin 17 (CDH17) in Cancer Progression via Wnt/β-Catenin Signalling Pathway: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 26(20), 9838. https://doi.org/10.3390/ijms26209838