title: The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries.
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.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grasso
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chapelle
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Salemme
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Aramu
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Russo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Vitale
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Verdun di Cantogno
authors.affiliation: Research Infrastructure, IRCCS Arcispedale Santa Maria Nuova, 42100 Reggio Emilia, Italy.
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Dallaglio
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.affiliation: Department of Bioscience and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Centonze
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Nanaocha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Lunardi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Sara
authors.identifier: 0000-0003-1248-6549
authors.initials: S
authors.lastname: Cabodi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Federica
authors.identifier: 0000-0003-4571-1060
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D'Annunzio University, Chieti-Pescara, 66100 Chieti, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lamolinara
authors.affiliation: Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D'Annunzio University, Chieti-Pescara, 66100 Chieti, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stramucci
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Enrico
authors.identifier: 0000-0002-4405-8357
authors.initials: E
authors.lastname: Moiso
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Paolo
authors.identifier: 0000-0001-8664-8630
authors.initials: P
authors.lastname: Provero
authors.affiliation: Scientific and Technology Pole, IRCCS MultiMedica, 20100 Milan, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Albini
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund 22100, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.affiliation: Molecular Medicine Program, European Institute of Oncology, 20100 Milan, Italy.|IFOM, The FIRC Institute for Molecular Oncology Foundation, 20100 Milan, Italy.|Department of Oncology and Hemato-oncology, University of Milan, 20100 Milan, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.affiliation: Molecular Medicine Program, European Institute of Oncology, 20100 Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertalot
authors.affiliation: Molecular Medicine Program, European Institute of Oncology, 20100 Milan, Italy.|Department of Oncology and Hemato-oncology, University of Milan, 20100 Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pece
authors.affiliation: Molecular Medicine Program, European Institute of Oncology, 20100 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tosoni
authors.affiliation: Molecular Medicine Program, European Institute of Oncology, 20100 Milan, Italy.|IFOM, The FIRC Institute for Molecular Oncology Foundation, 20100 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.affiliation: Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D'Annunzio University, Chieti-Pescara, 66100 Chieti, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Stefano
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Turco
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Defilippi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020744:rac GTP-Binding Proteins; C532615:SRCIN1 protein, human; C508053:ERBB2 protein, human