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

Silvia Grasso, Jennifer Chapelle, Vincenzo Salemme, Simona Aramu, Isabella Russo, Nicoletta Vitale, Ludovica Verdun di Cantogno, Katiuscia Dallaglio, Isabella Castellano, Augusto Amici, Giorgia Centonze, Nanaocha Sharma, Serena Lunardi, Sara Cabodi, Federica Cavallo, Alessia Lamolinara, Lorenzo Stramucci, Enrico Moiso, Paolo Provero, Adriana Albini, Anna Sapino, Johan Staaf, Pier Paolo Di Fiore, Giovanni Bertalot, Salvatore Pece, Daniela Tosoni, Stefano Confalonieri, Manuela Iezzi, Paola Di Stefano, Emilia Turco and Paola Defilippi ()
Additional contact information
Silvia Grasso: University of Torino
Jennifer Chapelle: University of Torino
Vincenzo Salemme: University of Torino
Simona Aramu: University of Torino
Isabella Russo: University of Torino
Nicoletta Vitale: University of Torino
Ludovica Verdun di Cantogno: Candiolo Cancer Institute-FPO, IRCCS
Katiuscia Dallaglio: Research Infrastructure, IRCCS Arcispedale Santa Maria Nuova
Isabella Castellano: Candiolo Cancer Institute-FPO, IRCCS
Augusto Amici: University of Camerino
Giorgia Centonze: University of Torino
Nanaocha Sharma: University of Torino
Serena Lunardi: University of Torino
Sara Cabodi: University of Torino
Federica Cavallo: University of Torino
Alessia Lamolinara: Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D’Annunzio University
Lorenzo Stramucci: Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D’Annunzio University
Enrico Moiso: University of Torino
Paolo Provero: University of Torino
Adriana Albini: Scientific and Technology Pole, IRCCS MultiMedica
Anna Sapino: Candiolo Cancer Institute-FPO, IRCCS
Johan Staaf: Lund University
Pier Paolo Di Fiore: Molecular Medicine Program, European Institute of Oncology
Giovanni Bertalot: Molecular Medicine Program, European Institute of Oncology
Salvatore Pece: Molecular Medicine Program, European Institute of Oncology
Daniela Tosoni: Molecular Medicine Program, European Institute of Oncology
Stefano Confalonieri: Molecular Medicine Program, European Institute of Oncology
Manuela Iezzi: Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D’Annunzio University
Paola Di Stefano: University of Torino
Emilia Turco: University of Torino
Paola Defilippi: University of Torino

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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 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.

Date: 2017
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DOI: 10.1038/ncomms14797

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