ArticleThe Biochemical journal2009
Nuclear translocation and signalling of L1-CAM in human carcinoma cells requires ADAM10 and presenilin/gamma-secretase activity.
Article in The Biochemical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- L1 Cell Adhesion Molecule in Cancer, a Systematic Review on Domain-Specific Functions.International journal of molecular sciences · 2019Pooled it
- Clinical Significance of Soluble L1CAM Serum Levels in Patients with High-Risk Endometrial Cancer.Biomedicines · 2025Article
- The emerging role of human transmembrane RGD-based counter-receptors of integrins in health and disease.Cellular & molecular biology letters · 2025Review
- A Necessary Role for Cyclin D2 Induction During Colon Cancer Progression Mediated by L1.Cells · 2024Article
- Functional Relationships between L1CAM, LC3, ATG12, and Aβ.International journal of molecular sciences · 2024Article
- Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities.Biomolecules · 2024Article
- L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease.Heliyon · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage.Cells · 2022Review
- Tryptophan hydroxylase 1 drives glioma progression by modulating the serotonin/L1CAM/NF-κB signaling pathway.BMC cancer · 2022Article
- Role of L1CAM in retinoblastoma tumorigenesis: identification of novel therapeutic targets.Molecular oncology · 2022Article
- L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling.Journal of experimental & clinical cancer research : CR · 2021Article
- Article
- Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells.Journal of clinical medicine · 2020Review
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Structural Perspectives on Extracellular Recognition and Conformational Changes of Several Type-I Transmembrane Receptors.Frontiers in molecular biosciences · 2020Review
- NOTCH2/NOTCH3/DLL3/MAML1/ADAM17 signaling network is associated with ovarian cancer.Oncology letters · 2019Article
- Review
- L1cam-mediated developmental processes of the nervous system are differentially regulated by proteolytic processing.Scientific reports · 2019Article
- An ankyrin-binding motif regulates nuclear levels of L1-type neuroglian and expression of the oncogeneThe Journal of biological chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L1-CAM (L1 cell-adhesion molecule), or more simply L1, plays an important role in the progression of human carcinoma. Overexpression promotes tumour-cell invasion and motility, growth in nude mice and tumour metastasis. It is feasible that L1-dependent signalling contributes to these effects. However, little is known about its mechanism in tumour cells. We reported previously that L1 is cleaved by ADAM (a disintegrin and metalloprotease) and that the cytoplasmic part is essential for L1 function. Here we analysed more closely the role of proteolytic cleavage in L1-mediated nuclear signalling. Using OVMz carcinoma cells and L1-transfected cells as a model, we found that ADAM10-mediated cleavage of L1 proceeds in lipid raft and non-raft domains. The cleavage product, L1-32, is further processed by PS (presenilin)/gamma-secretase to release L1-ICD, an L1 intracellular domain of 28 kDa. Overexpression of dominant-negative PS1 or use of a specific gamma-secretase inhibitor leads to an accumulation of L1-32. Fluorescence and biochemical analysis revealed a nuclear localization for L1-ICD. Moreover, inhibition of ADAM10 and/or gamma-secretase blocks nuclear translocation of L1-ICD and L1-dependent gene regulation. Overexpression of recombinant L1-ICD mediates gene regulation in a similar manner to full-length L1. Our results establish for the first time that regulated proteolytic processing by ADAM10 and PS/gamma-secretase is essential for the nuclear signalling of L1 in human carcinoma cell lines.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.