ArticleNature communications2015
PH motifs in PAR1&2 endow breast cancer growth.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Cell-cell junction gene signatures as subtype-specific prognostic biomarkers in breast cancer.PloS one · 2026Article
- GPCRs interaction with LGR5: Implications to cancer stemness.Journal of Cancer · 2026Article
- PARInternational journal of molecular sciences · 2025Article
- New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Involvement of Protease-Activated Receptor2 Pleckstrin Homology Binding Domain in Ovarian Cancer: Expression in Fallopian Tubes and Drug Design.Biomedicines · 2024Article
- PH-binding motifs as a platform for drug design: Lessons from protease-activated receptors; PARs.Oncoscience · 2024Article
- TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.Cancers · 2023Article
- Review
- GPCR Partners as Cancer Driver Genes: Association with PH-Signal Proteins in a Distinctive Signaling Network.International journal of molecular sciences · 2021Review
- Osteoblasts Promote Prostate Cancer Cell Proliferation Through Androgen Receptor Independent Mechanisms.Frontiers in oncology · 2021Article
- Design and Evaluation of Heterobivalent PAR1-PAR2 Ligands as Antagonists of Calcium Mobilization.ACS medicinal chemistry letters · 2019Article
- GPCR Modulation in Breast Cancer.International journal of molecular sciences · 2018Review
- Transcriptional Landscape of PARs in Epithelial Malignancies.International journal of molecular sciences · 2018Review
- Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.Journal of thrombosis and haemostasis : JTH · 2018Article
- Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach.International journal of molecular sciences · 2018Review
- Positive crosstalk between EGFR and the TF-PAR2 pathway mediates resistance to cisplatin and poor survival in cervical cancer.Oncotarget · 2018Article
- Article
- G Protein-Coupled Receptors in Cancer.International journal of molecular sciences · 2016Review
- PH-domains as central modulators driving tumor growth.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.
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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.