# Wnt / β-catenin

Source: https://onco.cc/pathways/wnt/  
OnCo record `wnt` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Wnt/β-catenin is a developmental pathway hijacked by colorectal cancer. Normally a destruction complex keeps β-catenin low; losing APC lets it flood the nucleus and drive growth genes.

## Summary

Without Wnt, β-catenin is phosphorylated by the destruction complex (APC, AXIN, GSK3β, CK1) and degraded. Wnt binding to Frizzled/LRP5/6 disables the complex; β-catenin accumulates, enters the nucleus, and with TCF/LEF drives MYC, cyclin D1, LGR5, AXIN2. APC loss initiates ~80% of colorectal cancers; CTNNB1 mutations occur in HCC, endometrial, and desmoid tumours; RNF43/RSPO alterations define a ligand-dependent subset. Wnt is also immunosuppressive (excludes dendritic cells). Drugs have been hard: porcupine inhibitors for RSPO/RNF43 tumours, tankyrase inhibitors, and nirogacestat (gamma-secretase, desmoid) are the closest.

## Fields

- Kind: Pathway
- Last checked: 2026-09-04
- Analogy: β-catenin is a messenger constantly being shredded by a committee (APC and friends). A Wnt signal tells the committee to stand down. Colorectal cancer fires the committee (APC loss), so the messenger runs unchecked into the nucleus.
- Interventions: Porcupine inhibitors (RSPO-fusion / RNF43-mutant tumours, trials); Gamma-secretase inhibitor nirogacestat in desmoid tumours (approved 2023); Tankyrase inhibitors (preclinical/early); Indirect: chemoprevention with aspirin/COX-2 in Lynch and FAP

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Wnt_signaling_pathway
- Wikipedia: https://en.wikipedia.org/wiki/Wnt_signaling_pathway

## Connected records

- cancers: [Adrenocortical carcinoma](https://onco.cc/cancers/adrenocortical/), [Ampullary cancer (ampulla of Vater)](https://onco.cc/cancers/ampullary/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Craniopharyngioma](https://onco.cc/cancers/craniopharyngioma/), [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Familial adenomatous polyposis-associated colorectal cancer](https://onco.cc/cancers/fap-associated-colorectal-cancer/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Hepatoblastoma](https://onco.cc/cancers/hepatoblastoma/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors](https://onco.cc/cancers/ipmn-cystic-precursors/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [Pancreatic acinar cell carcinoma](https://onco.cc/cancers/pancreatic-acinar-cell-carcinoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Pancreatoblastoma](https://onco.cc/cancers/pancreatoblastoma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Small intestine cancer (small bowel adenocarcinoma)](https://onco.cc/cancers/small-bowel/), [Solid pseudopapillary neoplasm of the pancreas](https://onco.cc/cancers/solid-pseudopapillary-neoplasm/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/), [WNT-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-wnt/)
- technologies: [Chemoprevention & risk-reducing surgery](https://onco.cc/technologies/chemoprevention/)
- targets: [AMER1](https://onco.cc/targets/amer1/), [APC](https://onco.cc/targets/apc/), [CTNNB1](https://onco.cc/targets/ctnnb1/), [Glypican-3](https://onco.cc/targets/gpc3/), [LGR5](https://onco.cc/targets/lgr5-gene/), [LRP5](https://onco.cc/targets/lrp5/), [MYC](https://onco.cc/targets/myc-gene/), [RNF43](https://onco.cc/targets/rnf43/), [RSPO2](https://onco.cc/targets/rspo2/), [RSPO3](https://onco.cc/targets/rspo3/), [TCF7L2](https://onco.cc/targets/tcf7l2/)
- terms: [Adenoma-carcinoma sequence](https://onco.cc/terms/adenoma-carcinoma-sequence/), [Cancer stem cell theory and phenotypic plasticity](https://onco.cc/terms/cancer-stem-cell-theory/), [Colibactin](https://onco.cc/terms/colibactin/), [Consensus molecular subtypes (CMS1-4)](https://onco.cc/terms/cms-subtypes/), [Hallmark: evading growth suppressors](https://onco.cc/terms/evading-growth-suppressors/), [LGR5](https://onco.cc/terms/lgr5/), [R-spondin fusion](https://onco.cc/terms/rspo-fusion/), [Signalling pathway](https://onco.cc/terms/signalling-pathway/), [Stem cell](https://onco.cc/terms/stem-cell/)
- drugs: [Nirogacestat](https://onco.cc/drugs/nirogacestat/)
- trials: [DeFi](https://onco.cc/trials/defi/)
- key papers: [Clinical sequencing defines the genomic landscape of metastatic colorectal cancer](https://onco.cc/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer](https://onco.cc/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/), [Genetic alterations during colorectal-tumor development](https://onco.cc/key-papers/paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988/), [Genetic mechanisms of immune evasion in colorectal cancer](https://onco.cc/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/), [Genomic analyses identify molecular subtypes of pancreatic cancer](https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/), [Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer](https://onco.cc/key-papers/paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021/), [Genomic characterization of malignant progression in neoplastic pancreatic cysts](https://onco.cc/key-papers/paper-noe-cyst-malignant-progression-genomics-nat-commun-2020/), [Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate](https://onco.cc/key-papers/paper-pandey-gallbladder-elf3-nat-commun-2020/), [Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/), [Recurrent R-spondin fusions in colon cancer](https://onco.cc/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia](https://onco.cc/key-papers/paper-crockett-nagtegaal-serrated-neoplasia-gastroenterology-2019/), [The consensus molecular subtypes of colorectal cancer](https://onco.cc/key-papers/paper-cms-guinney-nat-med-2015/), [Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways](https://onco.cc/key-papers/paper-wu-pancreatic-cyst-exomes-rnf43-pnas-2011/), [Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets](https://onco.cc/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- people: [Eric R. Fearon](https://onco.cc/people/eric-fearon/), [Kenneth W. Kinzler](https://onco.cc/people/kenneth-kinzler/)
- ideas: [Macrocyclic peptides to cover protein surfaces that pills cannot](https://onco.cc/ideas/idea-bio1-macrocycle-ppi-campaign/)
- pathways: [Breast cancer (KEGG map)](https://onco.cc/pathways/breast-cancer-signalling/), [Cancer stem cells & phenotypic plasticity](https://onco.cc/pathways/cancer-stem-cells-plasticity/), [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [Gastric cancer (KEGG map)](https://onco.cc/pathways/gastric-cancer-signalling/), [Hedgehog signalling](https://onco.cc/pathways/hedgehog/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [MYC](https://onco.cc/pathways/myc/), [Proteoglycans in cancer](https://onco.cc/pathways/proteoglycans-in-cancer/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/)

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JSON: https://onco.cc/api/v1/entities/wnt.json