The Rap2B small GTPase is an oncogene that is expressed in a variety of cancers, but also regulates cell motility, adhesion, and actin cytoskeleton dynamics. Its effects on actin remodeling are particularly interesting as dysfunction of actin or Rap individually has been linked to intestinal diseases like colitis and colorectal cancer (CRC). In a recent study, Di et. al. identified a potential signaling axis involving Rap2B-plectin-F-actin in the progression of CRC. Preliminary studies by the group examined CRC versus non-tumor samples from the Cancer Genome Atlas via IHC and tissue microarray, and the results showed an increase in Rap2B expression in CRC samples, which was also associated with worse survival in CRC patients. They then utilized an intestine-specific knockout (IEC-KO) Rap2B mouse model to investigate its role in CRC and colitis. While these mice developed with normal intestinal features, when exposed to colonotropic mutagens to promote colitis, the Rap2B IEC-KO mice displayed a reduced number of colon tumors and diminished histological and pathological characteristics associated with colitis. RNAseq studies identified plectin as an interacting partner of interest. Additional molecular studies showed that Rap2B controls plectin expression. Upregulation of plectin acts downstream to decrease F-actin polymerization but not total actin levels. Importantly, altering F-actin levels through intervention with latrunculin B reversed the effects of Rap2B knockout on CRC. Collectively, these studies identified an important signaling process involving Rap2B, plectin, and F-actin in CRC and may be the basis for future therapeutics. Cytoskeleton Inc.’s G-Actin/F-actin In Vivo Assay Biochem Kit (Cat. # BK037) played a critical role in examining Rap2B’s and plectin’s mechanistic effects on the actin cytoskeleton.
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G-Actin/F-actin In Vivo Assay Biochem Kit (Cat. # BK037)
