Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12489
Title: RHOA inactivation enhances Wnt signalling and promotes colorectal cancer.
Authors: Rodrigues, Paulo;Macaya, Irati;Bazzocco, Sarah;Mazzolini, Rocco;Andretta, Elena;Dopeso, Higinio;Mateo-Lozano, Silvia;Bilić, Josipa;Cartón-García, Fernando;Nieto, Rocio;Suárez-López, Lucia;Afonso, Elsa;Landolfi, Stefania;Hernandez-Losa, Javier;Kobayashi, Kazuto;Cajal, Santiago Ramón Y;Tabernero, Josep;Tebbutt, Niall C;Mariadason, John M;Schwartz, Simo;Arango, Diego
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.
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.
Department of Pathology, Vall d'Hebron Hospital, Passeig Vall d'Hebron, 119-129, Barcelona 08035, Spain.
Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, 119-129, Barcelona 08035, Spain.
Ludwig Institute for Cancer Research, Melbourne-Branch, Austin Health, Heidelberg, Victoria 3084, Australia.
Issue Date: 21-Nov-2014
Citation: Nature Communications 2014; 5(): 5458
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.
Internal ID Number: 25413277
URI: http://ahro.austin.org.au/austinjspui/handle/1/12489
DOI: 10.1038/ncomms6458
URL: http://www.ncbi.nlm.nih.gov/pubmed/25413277
Type: Journal Article
Appears in Collections:Journal articles

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