RHOA inactivation enhances Wnt signalling and promotes colorectal cancer Academic Article uri icon

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

  • 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

publication date

  • December 2014