ArticleProceedings of the National Academy of Sciences of the United States of America2006
Targeting AMAP1 and cortactin binding bearing an atypical src homology 3/proline interface for prevention of breast cancer invasion and metastasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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
54 citing papers in PubMed, 109 citations in OpenAlex.
- Prognostic Significance of Cdc42 Expression in Colorectal Cancer and Its Concordance Between Primary Tumors and Matched Metastases: A Retrospective Observational Study.Journal of clinical medicine · 2026Article
- Definition and Discovery of Tandem SH3-Binding Motifs Interacting with Members of the p47Biomolecules · 2025Article
- ASAP1 Promotes Epithelial to Mesenchymal Transition by Activating the TGFβ Pathway in Papillary Thyroid Cancer.Cancer medicine · 2025Article
- Plasticity and Tumor Microenvironment in Pancreatic Cancer: Genetic, Metabolic, and Immune Perspectives.Cancers · 2024Review
- New Regulatory roles for Human Serum Amyloid A.International journal of research in oncology · 2024Article
- The conformation of the nSrc specificity-determining loop in the Src SH3 domain is modulated by a WX conserved sequence motif found in SH3 domains.Frontiers in molecular biosciences · 2024Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
- Integrative Analysis Identifies Multi-Omics Signatures That Drive Molecular Classification of Uveal Melanoma.Cancers · 2021Article
- Scanning Protein Surfaces with DNA-Encoded Libraries.ChemMedChem · 2021Review
- An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism.Nature communications · 2021Article
- High expression of CIN85 promotes proliferation and invasion of human esophageal squamous cell carcinoma.Molecular medicine reports · 2021Article
- A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways.Journal of Cancer · 2021Article
- Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells.Nanomaterials (Basel, Switzerland) · 2020Article
- Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome.PloS one · 2019Article
- A C-Terminal Fragment of Chlorotoxin Retains Bioactivity and Inhibits Cell Migration.Frontiers in pharmacology · 2019Article
- Epithelial-specific histone modification of the miR-96/182 locus targeting AMAP1 mRNA predisposes p53 to suppress cell invasion in epithelial cells.Cell communication and signaling : CCS · 2018Article
- Arf6 and its ZEB1-EPB41L5 mesenchymal axis are required for both mesenchymal- and amoeboid-type invasion of cancer cells.Small GTPases · 2018Article
- Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells.Oncology letters · 2018Article
- Frequent overexpression of AMAP1, an Arf6 effector in cell invasion, is characteristic of the MMTV-PyMT rather than the MMTV-Neu human breast cancer model.Cell communication and signaling : CCS · 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
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Invasive potentials of carcinomas greatly contribute to their metastasis, which is a major threat in most cancers. We have recently shown that Arf6 plays a pivotal role in breast cancer invasive activities and identified AMAP1 as an effector of GTP-Arf6 in invasion. Expression of AMAP1 correlates well with invasive phenotypes of primary tumors of the human breast. We also have shown that AMAP1 functions by forming a trimeric protein complex with cortactin and paxillin. In this complex, AMAP1 binds to the src homology 3 (SH3) domain of cortactin via its proline-rich peptide, SKKRPPPPPPGHKRT. SH3 domains are known to bind generally to the proline-rich ligands with a one-to-one stoichiometry. We found that AMAP1/cortactin binding is very atypical in its stoichiometry and interface structure, in which one AMAP1 proline-rich peptide binds to two cortactin SH3 domains simultaneously. We made a cell-permeable peptide derived from the AMAP1 peptide, and we show that this peptide specifically blocks AMAP1/cortactin binding, but not other canonical SH3/proline bindings, and effectively inhibits breast cancer invasion and metastasis. Moreover, this peptide was found to block invasion of other types of cancers, such as glioblastomas and lung carcinomas. We also found that a small-molecule compound, UCS15A, which was previously judged as a weak inhibitor against canonical SH3/proline bindings, effectively inhibits AMAP1/cortactin binding and breast cancer invasion and metastasis. Together with fine structural analysis, we propose that the AMAP1/cortactin complex, which is not detected in normal mammary epithelial cells, is an excellent drug target for cancer therapeutics.
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.