Exogenous expression of wild-type RalGAP, but not the GAP activity-deficient mutant of RalGAP, suppressed migration and invasion of multiple PCa cell lines and was phenocopied by pharmacological inhibition of RalA/B.
The results show the invasion and migration abilities of 4T-1 and SKBR3 cells are significantly enhanced by the presence of HA35 but inhibited by HA117 in both 2D monolayers and 3D spheroids.
Re-expression of srGAP3 in a subset of these cell lines inhibits both anchorage-independent growth and cell invasion in a GAP-dependent manner, and this is accompanied by an increase in phosphorylation of the ezrin/radixin/moesin (ERM) family proteins and myosin light chain 2 (MLC2).
Connexin26 (Cx26), a component of GAP junctions and until recently believed to be a tumor suppressor gene, has been shown to play an important role in lymphatic invasion as well as lymph node and distant metastases in squamous lung cancer and breast cancer.