Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6458
Keywords
-
Categories
Funding
- Spanish Ministry for Economy and Competitiveness [CP05/00256, TRA2009 0093, SAF2008 00789, PI12/03103, PI12/01095]
- Association for International Cancer Research [AICR13-0245]
- Fundacion Mutua Madrilena
- Agencia de Gestio d'Ajuts Universitaris i de Recerca [SGR 157]
- Worldwide Cancer Research [13-0245] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [25640037] Funding Source: KAKEN
Ask authors/readers for more resources
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/beta-catenin signalling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of beta-catenin from the membrane to the nucleus and enhanced Wnt/beta-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/beta-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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available