ArticleProceedings of the National Academy of Sciences of the United States of America2021
Parsing β-catenin's cell adhesion and Wnt signaling functions in malignant mammary tumor progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo.Science advances · 2026Article
- FGFR1 Promotes Malignant Progression in Lung Squamous Cell Carcinoma Through Activation of Wnt/β-Catenin Signaling.Cancer medicine · 2026Article
- Integrated multi-omics analysis reveals comprehensive metabolism-driven tumor heterogeneity and immune microenvironment in hepatocellular carcinomas.Scientific reports · 2026Article
- Decoding the regulatory code: O-GlcNAcylation in epithelial-mesenchymal transition (EMT).The Journal of biological chemistry · 2026Review
- Effects of SOX10 on the proliferative, invasive, migratory, and epithelial-mesenchymal transition abilities of triple-negative breast cancer cells.Frontiers in oncology · 2026Article
- Integrated molecular data analysis confirms PDK1 as a candidate risk factor in ALS pathophysiology.Molecular brain · 2025Article
- Widespread 3' UTR splicing regulates expression of oncogene transcripts through multiple mechanisms.Nucleic acids research · 2025Article
- The developmental factor TBX3 engages with the Wnt/β-catenin transcriptional complex in colorectal cancer to regulate metastasis genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial-Mesenchymal Transition.Cancers · 2025Review
- Targeting the Key Signaling Pathways in Breast Cancer: From Molecular Mechanism to Therapeutic Interventions.Recent patents on anti-cancer drug discovery · 2025Review
- DNAJB4/HLJ1 deficiency sensitizes diethylnitrosamine-induced hepatocarcinogenesis with peritumoral STAT3 activation.Cell biology and toxicology · 2024Article
- Prognostic Protein Biomarker Screening for Thyroid Carcinoma Based on Cancer Proteomics Profiles.Biomedicines · 2024Article
- Ketogenic diet does not promote triple-negative and luminal mammary tumor growth and metastasis in experimental mice.Clinical & experimental metastasis · 2024Article
- Intestinal permeability correlates with disease activity and DNA methylation changes in lupus patients.Clinical immunology (Orlando, Fla.) · 2024Article
- The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.Science advances · 2024Article
- Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation.American journal of cancer research · 2024Article
- Implementing an On-Slide Molecular Classification of Gastric Cancer: A Tissue Microarray Study.Cancers · 2023Article
- Hsa-microRNA-1249-3p/Homeobox A13 axis modulates the expression of β-catenin gene in human epithelial cells.Scientific reports · 2023Article
- Ezh2 promotes mammary tumor initiation through epigenetic regulation of the Wnt and mTORC1 signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During malignant progression, epithelial cancer cells dissolve their cell-cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell-cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of β-catenin's transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)-PyMT mouse model of metastatic breast cancer, we compared the complete elimination of β-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of β-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of β-catenin's transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial-mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by β-catenin's transcriptional activities upon stimulation with Wnt3a or during TGF-β-induced EMT. Our results uncouple the signaling from the adhesion function of β-catenin and underline the importance of Wnt/β-catenin-dependent transcription in malignant tumor progression of breast cancer.
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