ArticleCell death & disease2022
RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1.Cell death & disease · 2026Article
- Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight.Angewandte Chemie (International ed. in English) · 2026Article
- Rhomboid protease Rhbdl2 regulates macrophage recruitment and wound regeneration in zebrafish.bioRxiv : the preprint server for biology · 2026Article
- Research progress of OTUD7B: from structural function and disease mechanisms to clinical translation.Frontiers in immunology · 2026Review
- Primary Follicle Paces Fish Ovarian Maturation Developmental Progression via the Enhancement of Notch and mTOR.Biology · 2025Article
- Transcriptomic Insights into Late-Life Depression and the Role of Environmental Drinking Water Composition: A Study on 18-Month-Old Mice.International journal of molecular sciences · 2025Article
- Synthesis and evaluation ofSynlett : accounts and rapid communications in synthetic organic chemistry · 2025Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Knockdown of CCNB2 inhibits the tumorigenesis of gastric cancer by regulation of the PI3K/Akt pathway.Scientific reports · 2025Article
- Reduced OTUD7B expression correlates with poor prognosis in PTCL via non-canonical NF-κB.International journal of hematology · 2025Article
- OTUD7B is a new deubiquitinase targeting p53.Theranostics · 2025Article
- Signatures of tumor microenvironment-related genes and long noncoding RNAs predict poor prognosis in osteosarcoma.PloS one · 2025Article
- MYBBP1A‑mediated IGFBP4 promoter methylation promotes epithelial‑mesenchymal transition and metastasis through activation of NOTCH pathway in liver cancer.International journal of oncology · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- TRIM59/RBPJ positive feedback circuit confers gemcitabine resistance in pancreatic cancer by activating the Notch signaling pathway.Cell death & disease · 2024Article
- Review
- Rhomboid-like 2 correlated with TME infiltration inhibits cuproptosis-related genes and drives malignant phenotype in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Comprehensive analysis and experimental verification of the mechanism of anoikis related genes in pancreatic cancer.Heliyon · 2024Article
- OTUD7B knockdown inhibits proliferation and autophagy through AKT/mTOR signaling pathway in human prostate cancer cell.Discover oncology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.
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