title: RHOA inactivation enhances Wnt signalling and promotes colorectal cancer.
abstract: Activation of the small GTPase RHOA has strong oncogenic effects in many tumour types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signalling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signalling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared with primary human colon tumours. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signalling and characterized the role of RHOA as a novel tumour suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumour progression and metastasis.
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Paulo
authors.initials: P
authors.lastname: Rodrigues
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Irati
authors.initials: I
authors.lastname: Macaya
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bazzocco
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Rocco
authors.initials: R
authors.lastname: Mazzolini
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Andretta
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Higinio
authors.initials: H
authors.lastname: Dopeso
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mateo-Lozano
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Josipa
authors.initials: J
authors.lastname: Bilić
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cartón-García
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Nieto
authors.affiliation: 1] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain [2] Group of Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: Suárez-López
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Elsa
authors.initials: E
authors.lastname: Afonso
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
authors.forename: Stefania
authors.initials: S
authors.lastname: Landolfi
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez-Losa
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Pathology, Vall d'Hebron Hospital, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón y Cajal
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, 119-129, Barcelona 08035, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne-Branch, Austin Health, Heidelberg, Victoria 3084, Australia.
authors.forename: Niall C
authors.initials: NC
authors.lastname: Tebbutt
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne-Branch, Austin Health, Heidelberg, Victoria 3084, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Mariadason
authors.affiliation: 1] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain [2] Group of Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
authors.forename: Simo
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: 1] Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain [2] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Arango
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein