Cell cycle regulators, such as
cyclins, are often upregulated in many proliferative disorders, and
Cyclin A2 is generally considered as a marker of aggressive
cancers. Our recent work, which revealed decreased expression of
Cyclin A2 upon
metastasis of
colorectal cancer, suggests a more complicated situation. Consistent with this, we identified a role for
Cyclin A2, via RhoA, in regulation of the actin cytoskeleton and the control of cell invasion.
Cyclin A2 also regulates spindle orientation which, when misoriented, could disrupt cell polarity and favor
cancer cell detachment from the
tumor as part of a transforming process, such as epithelial to mesenchymal transition (EMT). During EMT, cells undergo morphological and molecular changes toward a mesenchymal phenotype. Upregulation, or increased activity of some
Rho GTPases, such as Cdc42, Rac1 or RhoC, increases the invasive potential of these cells. This correlates with the inverse relationship between RhoA and RhoC activities we observed in an epithelial cell type. Altogether, these observations raise the possibility that
Cyclin A2 is instrumental in preventing EMT and therefore
cancers of epithelial tissues.