ArticleAmerican journal of cancer research2013
Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.
Article in American journal of cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The trial behind it
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Effects of NaCell biochemistry and biophysics · 2025Review
- Enhancing the Bioactivity of Bicyclic Peptides Targeted to Grb7-SH2 by Restoring Cell Permeability.Biomedicines · 2022Article
- Article
- Direct Interaction between Calmodulin and the Grb7 RA-PH Domain.International journal of molecular sciences · 2020Article
- Evaluation of Cyclic Peptide Inhibitors of the Grb7 Breast Cancer Target: Small Change in Cargo Results in Large Change in Cellular Activity.Molecules (Basel, Switzerland) · 2019Article
- Review
- RAC1 Takes the Lead in Solid Tumors.Cells · 2019Review
- Src homology 2 domains enhance tyrosine phosphorylationThe Journal of biological chemistry · 2018Article
- Breast Cancer in Latinas: A Focus on Intrinsic Subtypes Distribution.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Review
- Grb7 protein RA domain oligomerization.Journal of molecular recognition : JMR · 2017Article
- Shortened Penetratin Cell-Penetrating Peptide Is Insufficient for Cytosolic Delivery of a Grb7 Targeting Peptide.ACS omega · 2017Article
- RAC1 GTP-ase signals Wnt-beta-catenin pathway mediated integrin-directed metastasis-associated tumor cell phenotypes in triple negative breast cancers.Oncotarget · 2017Article
- Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target.Frontiers in molecular biosciences · 2017Article
- Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers.Nature communications · 2016Article
- Wnt-beta-catenin pathway signals metastasis-associated tumor cell phenotypes in triple negative breast cancers.Oncotarget · 2016Article
- Grb7 and Hax1 may colocalize partially to mitochondria in EGF-treated SKBR3 cells and their interaction can affect Caspase3 cleavage of Hax1.Journal of molecular recognition : JMR · 2016Article
- Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7.Scientific reports · 2016Article
- Rational design of novel N-alkyl-N capped biostable RNA nanostructures for efficient long-term inhibition of gene expression.Nucleic acids research · 2016Article
- Anti-tumor efficacy of BEZ235 is complemented by its anti-angiogenic effects via downregulation of PI3K-mTOR-HIF1alpha signaling in HER2-defined breast cancers.American journal of cancer research · 2016Article
- Grb7 gene amplification and protein expression by FISH and IHC in ovarian cancer.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.
Indexed as
Identifiers
23593540PMC3623837W181749071What Socratic 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 Socratic graph.