[en] RhoGTPases are key signaling molecules regulating main cellular functions such as migration, proliferation, survival, and gene expression through interactions with various effectors. Within the RhoA-related subclass, RhoA and RhoC contribute to several steps of tumor growth, and the regulation of their expression affects cancer progression. Our aim is to investigate their respective contributions to the acquisition of an invasive phenotype by using models of reduced or forced expression. The silencing of RhoC, but not of RhoA, increased the expression of genes encoding tumor suppressors, such as nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1), and decreased migration and the anchorage-independent growth in vitro. In vivo, RhoC small interfering RNA (siRhoC) impaired tumor growth. Of interest, the simultaneous knockdown of RhoC and NAG-1 repressed most of the siRhoC-related effects, demonstrating the central role of NAG-1. In addition of being induced by RhoC silencing, NAG-1 was also largely up-regulated in cells overexpressing RhoA. The silencing of RhoGDP dissociation inhibitor alpha (RhoGDIalpha) and the overexpression of a RhoA mutant unable to bind RhoGDIalpha suggested that the effect of RhoC silencing is indirect and results from the up-regulation of the RhoA level through competition for RhoGDIalpha. This study demonstrates the dynamic balance inside the RhoGTPase network and illustrates its biological relevance in cancer progression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ho, Thi Thanh Giang ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Stultiens, Audrey; Université de Liège - ULiège > Dpt des sciences biomédicales et Précliniques > Laboratoire de Biologie des Tissus Conjonctifs
Dubail, Johanne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Lapiere, Charles M; Université de Liège - ULiège
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Deroanne, Christophe ; Université de Liège - ULiège > Dept des Sciences biomédicales et précliniques > Laboratoire de Biologie des Tissus Conjonctifs
Language :
English
Title :
RhoGDI alpha-dependent balance between RhoA and RhoC is a key regulator of cancer cell tumorigenesis
Publication date :
2011
Journal title :
Molecular Biology of the Cell
ISSN :
1059-1524
eISSN :
1939-4586
Publisher :
American Society for Cell Biology, Bethesda, United States - Maryland
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