Related Experiment Video

Updated: Jul 16, 2026

Spheroid Assay to Measure TGF-β-induced Invasion
09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

A role for the scaffolding adapter GAB2 in breast cancer

Mohamed Bentires-Alj1, Susana G Gil, Richard Chan

  • 1Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, NRB 1030, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. mbentire@bidmc.harvard.edu

Nature Medicine
|December 22, 2005
PubMed

Insights

Grb2-associated binding protein 2 (GAB2) overexpression drives breast cancer cell proliferation and invasion. Targeting GAB2 may offer new therapeutic strategies for breast tumors, especially those overexpressing HER2.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Grb2-associated binding protein 2 (GAB2) gene is located in the 11q13-14 region, frequently amplified in human breast cancer.
  • GAB2 is overexpressed in breast cancer cell lines and primary tumors, but its role in mammary carcinogenesis is not well understood.

Purpose of the Study:

  • To investigate the functional role of GAB2 in mammary cell proliferation, invasion, and breast carcinogenesis.
  • To explore the molecular pathways and therapeutic potential associated with GAB2 in breast cancer.

Main Methods:

  • Assessed GAB2 effects on MCF10A mammary cell proliferation in 3D culture.
  • Investigated GAB2 coexpression with oncogenes (antiapoptotic and Neu/ErbB2/HER2) to observe cellular phenotypes.
  • Analyzed GAB2's impact on Neu-evoked breast carcinogenesis in mouse models.
  • Examined GAB2 amplification in human breast tumors.

Main Results:

  • GAB2 overexpression increased MCF10A cell proliferation.
  • Coexpression of GAB2 with antiapoptotic oncogenes led to lumenal filling; with Neu/HER2, it induced an invasive phenotype.
  • GAB2-mediated effects involved Shp2-Erk pathway hyperactivation.
  • GAB2 overexpression potentiated, while deficiency ameliorated, Neu-evoked breast carcinogenesis in mice.
  • GAB2 amplification was observed in some GAB2-overexpressing human breast tumors.

Conclusions:

  • GAB2 may be a key gene in the 11q13 amplicon and plays a significant role in mammary carcinogenesis.
  • Overexpression of GAB2 contributes to breast cancer progression.
  • Targeting GAB2 or its downstream pathways presents a potential therapeutic strategy for breast tumors overexpressing GAB2 and/or HER2.

More Related Videos

A 3D Spheroid Model as a More Physiological System for Cancer-Associated Fibroblasts Differentiation and Invasion In Vitro Studies06:27

A 3D Spheroid Model as a More Physiological System for Cancer-Associated Fibroblasts Differentiation and Invasion In Vitro Studies

Published on: August 8, 2019

Heteromulticellular Stromal Cells in Scaffold-free 3D Cultures of Epithelial Cancer Cells to Drive Invasion09:18

Heteromulticellular Stromal Cells in Scaffold-free 3D Cultures of Epithelial Cancer Cells to Drive Invasion

Published on: April 4, 2025

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...