Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 607–615 | Cite as

GRB7 is required for triple-negative breast cancer cell invasion and survival

  • Orsi Giricz
  • Verónica Calvo
  • Stephanie C. Pero
  • David N. Krag
  • Joseph A. Sparano
  • Paraic A. Kenny
Preclinical Study


Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful biomarkers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines—MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.


GRB7 Adapter proteins Triple-negative breast cancer Tumor cell invasion Receptor tyrosine kinase signaling 



OG and PK were supported by a postdoctoral fellowship (KG091136) and a Career Catalyst Award (KG100888) from the Susan G. Komen for the Cure Foundation. VC was supported by a postdoctoral fellowship from the Fundacion Alfonso Martin Escudero. SP and DK were supported by The National Cancer Institute (R01 CA80790) and in part by the SD Ireland Cancer Research Foundation. We gratefully acknowledge the Integrative Cancer Biology Program of the National Cancer Institute for provision of cell lines from the ICBP45 kit for use in this study.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Orsi Giricz
    • 1
  • Verónica Calvo
    • 1
  • Stephanie C. Pero
    • 4
  • David N. Krag
    • 4
  • Joseph A. Sparano
    • 2
    • 3
  • Paraic A. Kenny
    • 1
  1. 1.Department of Developmental and Molecular BiologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of Medicine and OncologyAlbert Einstein College of MedicineBronxUSA
  3. 3.Montefiore Medical CenterBronxUSA
  4. 4.Department of Surgery and Vermont Cancer CenterUniversity of VermontBurlingtonUSA

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