ArticleSmall GTPases
Rap1 and its regulatory proteins: the tumor suppressor, oncogene, tumor suppressor gene axis in head and neck cancer.
Article in Small GTPases. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- A Rare Case of Cutaneous Metastasis From Oral Squamous Cell Carcinoma (OSCC) and the Possible Role of GALR2 as a Biomarker: A Case Report.Clinical case reports · 2026Article
- Targeting EZH2-driven cholesterol metabolic vulnerability through Napabucasin suppresses ovarian cancer metastasis.Cell death & disease · 2026Article
- Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025Review
- CD147 regulates the Rap1 signaling pathway to promote proliferation, migration, and invasion, and inhibit apoptosis in colorectal cancer cells.Scientific reports · 2025Article
- CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression.Frontiers in pharmacology · 2024Article
- Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients.Cancers · 2021Article
- Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.The Journal of experimental medicine · 2021Article
- RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC.Journal of dental research · 2020Article
- Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.Experimental and therapeutic medicine · 2019Article
- Identification of potential key genes in esophageal adenocarcinoma using bioinformatics.Experimental and therapeutic medicine · 2019Article
- Identification of potential tissue-specific cancer biomarkers and development of cancer versus normal genomic classifiers.Oncotarget · 2017Article
- Article
- The Ras-related protein, Rap1A, mediates thrombin-stimulated, integrin-dependent glioblastoma cell proliferation and tumor growth.The Journal of biological chemistry · 2014Article
- EZH2: not EZHY (easy) to deal.Molecular cancer research : MCR · 2014Review
- The Histone Methyltransferase EZH2 Mediates Tumor Progression on the Chick Chorioallantoic Membrane Assay, a Novel Model of Head and Neck Squamous Cell Carcinoma.Translational oncology · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer, globally. Previously, we showed that Rap1GAP is a tumor suppressor gene that inhibits tumor growth, but promotes invasion in SCCHN. In this work, we discuss the role of Rap1 and Rap1GAP in SCCHN progression in the context of a microRNA-oncogene-tumor suppressor gene axis, and investigate the role of Rap1GAP in EZH2-mediated invasion. Loss of expression of microRNA-101 in SCCHN leads to upregulation of EZH2, a histone methyltransferase. Overexpression of EZH2 silences Rap1GAP via methylation, thereby promoting activation of its target, Rap1. This microRNA-controlled activation of Rap1, via EZH2-mediated silencing of Rap1GAP, is a novel mechanism of Rap1 regulation. In two independent SCCHN cell lines, downregulation of EZH2 inhibits proliferation and invasion. In both cell lines, stable knockdown of EZH2 (shEZH2) recovers Rap1GAP expression and inhibits proliferation. However, siRNA-mediated knockdown of Rap1GAP in these cells rescues proliferation but not invasion. Thus, EZH2 promotes proliferation and invasion via Rap1GAP-dependent and -independent mechanisms, respectively. Although the studies presented here are in the context of SCCHN, our results may have broader implications, given that Rap1GAP acts as a tumor suppressor in pancreatic cancer, thyroid cancer, and melanoma.
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