ArticleAmerican journal of human genetics2012
RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 202 citations in OpenAlex.
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- HK2/VDAC1 Axis Regulates Malignant Progression of Esophageal Squamous Cell Carcinoma.Cancer medicine · 2026Article
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- A sterol-binding pocket in iRhom1 underlies paralog-specific regulation of the sheddase ADAM17.bioRxiv : the preprint server for biology · 2026Article
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Proteolytic dysregulation in the skin: insight from rare monogenic skin diseases.Cell and tissue research · 2026Review
- iRhom2 deletion protects against diabetic neuropathy by suppressing neuroinflammation.The Journal of pharmacology and experimental therapeutics · 2026Article
- Induction of CXCL8 by endoplasmic reticulum stress promotes migration and invasion of esophageal squamous cell carcinoma through activation of SMAD2/3.Molecular medicine reports · 2025Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Gastrointestinal Cancer Precursor Conditions and Their Detection.Hematology/oncology clinics of North America · 2024Review
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.Molecular cell · 2024Article
- Investigating iRHOM2-Associated Transcriptional Changes in Tylosis With Esophageal Cancer.Gastro hep advances · 2024Article
- Article
- Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.Journal of cell science · 2023Article
- A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.Cellular and molecular life sciences : CMLS · 2023Article
- iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells.Journal of cell science · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 12 institutions in 2 countries.
Funding
Abstract
Tylosis esophageal cancer (TOC) is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. We have previously localized the TOC locus to a small genomic interval within chromosomal region 17q25. Using a targeted capture array and next-generation sequencing, we have now identified missense mutations (c.557T>C [p.Ile186Thr] and c.566C>T [p.Pro189Leu] in RHBDF2, which encodes the inactive rhomboid protease RHBDF2 (also known as iRhom2), as the underlying cause of TOC. We show that the distribution of RHBDF2 in tylotic skin is altered in comparison with that in normal skin, and immortalized tylotic keratinocytes have decreased levels of total epidermal growth factor receptor (EGFR) and display an increased proliferative and migratory potential relative to normal cells, even when normal cells are stimulated with exogenous epidermal growth factor. It would thus appear that EGFR signaling is dysregulated in tylotic cells. Furthermore, we also show an altered localization of RHBDF2 in both tylotic and sporadic squamous esophageal tumors. The elucidation of a role of RHBDF2 in growth-factor signaling in esophageal cancer will help to determine whether targeting this pathway in chemotherapy for this and other squamous cell carcinomas will be effective.
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