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

Grasso, Silvia; Chapelle, Jennifer; Salemme, Vincenzo; Aramu, Simona; Russo, Isabella; Vitale, Nicoletta; Verdun di Cantogno, Ludovica; Dallaglio, Katiuscia; Castellano, Isabella and Amici, Augusto, et al. (2017) In Nature Communications 8.
Abstract

The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac... (More)

The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.

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@article{6ae3c336-9647-487d-ad99-37637f13c699,
  abstract     = {<p>The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.</p>},
  articleno    = {14797},
  author       = {Grasso, Silvia and Chapelle, Jennifer and Salemme, Vincenzo and Aramu, Simona and Russo, Isabella and Vitale, Nicoletta and Verdun di Cantogno, Ludovica and Dallaglio, Katiuscia and Castellano, Isabella and Amici, Augusto and Centonze, Giorgia and Sharma, Nanaocha and Lunardi, Serena and Cabodi, Sara and Cavallo, Federica and Lamolinara, Alessia and Stramucci, Lorenzo and Moiso, Enrico and Provero, Paolo and Albini, Adriana and Sapino, Anna and Staaf, Johan and Di Fiore, Pier Paolo and Bertalot, Giovanni and Pece, Salvatore and Tosoni, Daniela and Confalonieri, Stefano and Iezzi, Manuela and Di Stefano, Paola and Turco, Emilia and Defilippi, Paola},
  issn         = {2041-1723},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {03},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries},
  url          = {http://dx.doi.org/10.1038/ncomms14797},
  volume       = {8},
  year         = {2017},
}