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The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled

Silvia Grasso1, Jennifer Chapelle1, Vincenzo Salemme1

  • 1Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.

Nature Communications
|March 17, 2017
PubMed

Insights

The docking protein p140Cap improves survival in ERBB2-amplified breast cancer by reducing tumor growth and metastasis. p140Cap may predict response to anti-ERBB2 therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The role of the docking protein p140Cap in breast cancer progression and patient survival is not fully understood.
  • p140Cap is known to negatively regulate tumor cell characteristics, but its specific impact on ERBB2-amplified breast cancer requires further investigation.

Purpose of the Study:

  • To investigate the prognostic significance of p140Cap in ERBB2-amplified breast cancer.
  • To elucidate the molecular mechanisms by which p140Cap influences tumor progression and metastasis.
  • To evaluate p140Cap as a potential predictive biomarker for anti-ERBB2 therapies.

Main Methods:

  • Analysis of p140Cap status in ERBB2-amplified breast cancer patient cohorts.
  • Assessment of tumor onset, growth, and metastasis in the NeuT mouse model with varying p140Cap levels.
  • Investigation of p140Cap's interference with ERBB2-dependent signaling pathways, including Rac GTPase activation.

Main Results:

  • p140Cap-positive status in ERBB2-amplified breast cancer patients correlates with a lower probability of distant events and improved survival.
  • p140Cap suppresses ERBB2-positive tumor cell progression, hindering tumor initiation and growth in preclinical models.
  • p140Cap counteracts epithelial-mesenchymal transition, leading to reduced metastasis formation.
  • p140Cap interferes with ERBB2-mediated activation of Rac GTPase signaling pathways.

Conclusions:

  • p140Cap plays a crucial role in limiting the aggressiveness of ERBB2-amplified breast cancers.
  • p140Cap functions by modulating key molecular pathways involved in tumor progression and metastasis.
  • p140Cap holds potential as a predictive biomarker for patient response to targeted anti-ERBB2 therapies.

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