ArticleMolecular and cellular biology2001
Grb2 and Shc adapter proteins play distinct roles in Neu (ErbB-2)-induced mammary tumorigenesis: implications for human breast cancer.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 163 citations in OpenAlex.
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- p66Shc deletion confers apoptotic resistance to loss of EGFR-ERK signalling in neural stem cells.Cell death & disease · 2025Article
- Nonlinear progression during the occult transition establishes cancer lethality.Disease models & mechanisms · 2025Article
- Review
- The Visualization of Protein-Protein Interactions in Breast Cancer: Deployment Study in Pathological Examination.Acta histochemica et cytochemica · 2021Review
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- Modeling metastasis in mice: a closer look.Trends in cancer · 2021Review
- The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation.The Journal of biological chemistry · 2020Article
- SH3BGRL confers innate drug resistance in breast cancer by stabilizing HER2 activation on cell membrane.Journal of experimental & clinical cancer research : CR · 2020Article
- Microscaled proteogenomic methods for precision oncology.Nature communications · 2020Article
- Identification of functionally connected multi-omic biomarkers for Alzheimer's disease using modularity-constrained Lasso.PloS one · 2020Article
- The Effects of Pertuzumab and Its Combination with Trastuzumab on HER2 Homodimerization and Phosphorylation.Cancers · 2019Article
- HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3.Cancer research · 2018Article
- Organ-specific metastasis of breast cancer: molecular and cellular mechanisms underlying lung metastasis.Cellular oncology (Dordrecht, Netherlands) · 2018Review
- Emerging roles for LPP in metastatic cancer progression.Journal of cell communication and signaling · 2018Review
- Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity.Cancer science · 2018Article
- Aging Mouse Models Reveal Complex Tumor-Microenvironment Interactions in Cancer Progression.Frontiers in cell and developmental biology · 2018Review
- MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells.Scientific reports · 2017Article
- Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer.Hypoxia (Auckland, N.Z.) · 2017Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Amplification of the Neu (ErbB-2 or HER-2) receptor tyrosine kinase occurs in 20 to 30% of human mammary carcinomas, correlating with a poor clinical prognosis. We have previously demonstrated that four (Y1144 Y1201, Y1227 and Y1253) of the five known Neu autophosphorylation sites can independently mediate transforming signals. The transforming potential of two of these mutants correlates with their capacity to recruit Grb2 directly to Y1144 (YB) or indirectly through Shc to Y1227 (YD). Here, we demonstrate that these transformation-competent neu mutants activate extracellular signal-regulated kinases and stimulate Ets-2-dependent transcription. Although the transforming potential of three of these mutants (YB, YD, and YE) was susceptible to inhibition by Rap1A, a genetic antagonist of Ras, the transforming potential of YC was resistant to inhibition by Rap1A. To further address the significance of these ErbB-2-coupled signaling molecules in induction of mammary cancers, transgenic mice expressing mutant Neu receptors lacking the known autophosphorylation sites (NYPD) or those coupled directly to either Grb2 (YB) or Shc (YD) adapter molecules were derived. In contrast to the NYPD strains, which developed focal mammary tumors after a long latency period with low penetrance, all female mice derived from YB and YD strains rapidly developed mammary tumors. Although female mice from several independent YB or YD lines developed mammary tumors, the YB strains developed lung metastases at substantially higher rates than the YD strains. These observations argue that Grb2 and Shc play important and distinct roles in ErbB-2/Neu-induced mammary tumorigenesis and metastasis.
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