ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Rap1 stabilizes beta-catenin and enhances beta-catenin-dependent transcription and invasion in squamous cell carcinoma of the head and neck.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Selection and optimization strategy for Rap1-targeting single-domain antibodies as platelet activation markers.Research and practice in thrombosis and haemostasis · 2026Article
- CD147 regulates the Rap1 signaling pathway to promote proliferation, migration, and invasion, and inhibit apoptosis in colorectal cancer cells.Scientific reports · 2025Article
- A dynamic co-expression approach reveals Gins2 as a potential upstream modulator of HNSCC metastasis.Scientific reports · 2025Article
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Review
- SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.Frontiers in molecular biosciences · 2021Review
- Review
- The Mystery of Rap1 Suppression of Oncogenic Ras.Trends in cancer · 2020Review
- The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas.Cells · 2020Review
- 4E-BP1Cancer management and research · 2020Article
- The Mechanism of Rap1 Regulates N-cadherin to Control Neuronal Migration.Journal of molecular neuroscience : MN · 2019Article
- Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions.Molecular carcinogenesis · 2019Article
- Ras and Rap1: A tale of two GTPases.Seminars in cancer biology · 2019Review
- Characterization of TCF4-mediated oncogenic role in cutaneous squamous cell carcinoma.International journal of clinical and experimental pathology · 2019Article
- Role of miR-337-3p and its target Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells.Cancer biomarkers : section A of Disease markers · 2019Article
- Wnt3a expression is associated with poor prognosis of esophageal squamous cell carcinoma.Oncology letters · 2018Article
- RAPGEF5 Regulates Nuclear Translocation of β-Catenin.Developmental cell · 2018Article
- Roles of Rap1 signaling in tumor cell migration and invasion.Cancer biology & medicine · 2017Article
- Integrative genomic and functional analysis of human oral squamous cell carcinoma cell lines reveals synergistic effects of FAT1 and CASP8 inactivation.Cancer letters · 2016Article
- Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen.Journal of medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
purposeIn head and neck squamous cell carcinoma (HNSCC) cells, Rap1 shuttles between the nucleus and cytoplasm. Prior findings suggested that Rap1 may modulate the beta-catenin-independent Wnt pathway in some settings, but the role of Rap1 in beta-catenin-dependent Wnt signaling remains undefined. EXPERIMENTAL DESIGN AND
resultsWe observed that beta-catenin bound to active Rap1 in vitro and Rap1 activated beta-catenin/T-cell factor (TCF)-dependent transcription. Immunofluorescence studies showed that ectopic expression of Rap1 increased nuclear translocation of beta-catenin. Overexpression of active Rap1 facilitated an increase in beta-catenin-mediated transcription that was abrogated by dominant-negative TCF4. Conversely, small interfering RNA-mediated inhibition of endogenous Rap1 expression inhibited beta-catenin/TCF-mediated transcription as well as invasion of HNSCC. Furthermore, inhibition of Rap1 expression downregulated the expression of matrix metalloproteinase 7, a transcriptional target of beta-catenin/TCF. In HNSCC cells stably transfected with beta-catenin or treated with lithium chloride or Wnt3A to stabilize endogenous beta-catenin, inhibition of Rap1 expression led to decreases in the free pool of beta-catenin. Immunohistochemical studies of tissue from HNSCC patients revealed that increased beta-catenin intensity correlated with higher tumor stage. Furthermore, the prognostic effect of active Rap1 on tumor N stage was found to depend on cytosolic beta-catenin expression (P < 0.013). When beta-catenin is high, higher Rap1GTP intensity is associated with more advanced N stage.
conclusionsThe findings suggest that Rap1 enhances beta-catenin stability and nuclear localization. In addition to indicating that Rap1 has a significant role in regulating beta-catenin and beta-catenin-dependent progression to more advanced N-stage lesions, these data highlight Rap1 as a potential therapeutic target in HNSCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.