RHOA inactivation enhances Wnt signalling and promotes colorectal cancer

Paulo Rodrigues, Irati Macaya, Sarah Bazzocco, Rocco Mazzolini, Elena Andretta, Higinio Dopeso, Silvia Mateo-Lozano, Josipa Bilić, Fernando Cartón-García, Rocio Nieto, Lucia Suárez-López, Elsa Afonso, Stefania Landolfi, Javier Hernandez-Losa, Kazuto Kobayashi, Santiago Ramón y Cajal, Josep Tabernero, Niall C. Tebbutt, John M. Mariadason, Simo Schwartz and Diego Arango ()
Additional contact information
Paulo Rodrigues: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Irati Macaya: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Sarah Bazzocco: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Rocco Mazzolini: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Elena Andretta: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Higinio Dopeso: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Silvia Mateo-Lozano: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Josipa Bilić: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Fernando Cartón-García: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Rocio Nieto: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Lucia Suárez-López: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
Elsa Afonso: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona
Stefania Landolfi: Vall d’Hebron Hospital
Javier Hernandez-Losa: Vall d’Hebron Hospital
Kazuto Kobayashi: Institute of Biomedical Sciences, Fukushima Medical University School of Medicine
Santiago Ramón y Cajal: Vall d’Hebron Hospital
Josep Tabernero: Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona
Niall C. Tebbutt: Ludwig Institute for Cancer Research, Melbourne-Branch, Austin Health
John M. Mariadason: Ludwig Institute for Cancer Research, Melbourne-Branch, Austin Health
Simo Schwartz: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
Diego Arango: Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d’Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms6458 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6458

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6458

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().