ArticleEBioMedicine2018
Proteolytic cleavage of amyloid precursor protein by ADAM10 mediates proliferation and migration in breast cancer.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 58 citations in OpenAlex.
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- Androgen Effects on Amyloid Precursor Protein Processing Pathways in Cancer: A Systematic Review.Current issues in molecular biology · 2025Review
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- Single-cell transcriptomic analysis in clear cell renal cell carcinoma: Deciphering the role of APP within the tumour microenvironment.Journal of cellular and molecular medicine · 2024Article
- Upregulation of circRNA_0023685 promotes gastric cancer progression via a circRNA-miRNA-mRNA interaction network.American journal of cancer research · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Multi-omics identification of GPCR gene features in lung adenocarcinoma based on multiple machine learning combinations.Journal of Cancer · 2024Article
- Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo.Molecular cancer · 2023Article
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- circ3323 Motivates Host Gene to Promote the Aggressiveness of Bladder Cancer.Biochemical genetics · 2022Article
- Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media.International journal of molecular sciences · 2022Article
- Vav2 is a novel APP-interacting protein that regulates APP protein level.Scientific reports · 2022Article
- Accumulation of amyloid beta (Aβ) and amyloid precursor protein (APP) in tumors formed by a mouse xenograft model of inflammatory breast cancer.FEBS open bio · 2022Article
- FE65 in breast cancer and its clinicopathological significance.Breast cancer (Tokyo, Japan) · 2022Article
- Exploring the Early Stages of the Amyloid Aβ(1-42) Peptide Aggregation Process: An NMR Study.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer.International journal of molecular sciences · 2021Review
- The emerging role of β-secretases in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmyloid precursor protein (APP), best known for its association with Alzheimer disease, has recently been implicated in breast cancer progression. However, the precise mechanism involved remains unclear. Here, we investigated the role of APP proteolytic cleavage in breast cancer functions.
methodsThe presence of APP proteolytic cleavage products was examined in breast cancer cell lines. The functional roles of APP in breast cancer were studied in vitro and tumor xenograft model using siRNA. The effects of full length APP and the α-secretase cleaved ectodomain fragment, soluble APPα (sAPPα) were further investigated for their overexpression in breast cancers. The α-secretase involved was identified. The α-secretase expression together with APP was examined in clinical breast cancers.
resultsWe showed that APP underwent proteolytic cleavage in breast cancer cells to generate sAPPα. The sAPPα and full length protein mediated breast cancer migration and proliferation, but in different functional extent. This proteolytic cleavage was mediated by ADAM10. Downregulation of APP and ADAM10 brought about similar functional effects. Overexpression of sAPPα reversed the effects of ADAM10 downregulation. Interestingly, in patients with non-luminal breast cancers, APP and ADAM10 expression correlated with each other and their co-expression was associated with the worst outcome.
conclusionsThese results demonstrated the contributory role of APP cleavage on its oncogenic roles in breast cancer. ADAM10 was the key α-secretase. APP and ADAM10 co-expression was associated with worse survival in non-luminal breast cancers. Targeting of APP or its processing by ADAM10 might be a promising treatment option in these cancers.
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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.