CDC42SE2 modulates epithelial-mesenchymal transition and tumor metastasis in colorectal cancer through CDC42 and downstream IQGAP3 signaling

Abstract By GWAS and fine mapping study, SNP rs1010208 was identified to be a risk locus of colorectal cancer (CRC). By eQTL-based analysis of SNP rs1010208, gene CDC42SE2 was confirmed as potential target gene of SNP rs1010208. However, there was little research about CDC42SE2 and CRC, while CDC42SE2 was demonstrated to be associated with patient prognosis and tumor onset risk. Here we aimed to investigate the role of CDC42SE2 on CRC progression. CDC42SE2 expression in CRC tissue, adjacent normal tissue and CRC cell lines and its relationship with clinicopathological parameters were investigated. In vitro and in vivo assays were used to explore the function of CDC42SE2 in the progression of CRC. The study showed that CDC42SE2 was down-expressed in CRC tissues and associated with poor prognosis and high TNM stages. Overexpression of CDC42SE2 can inhibit the proliferation, metastasis and invasion ability and increase the apoptosis ratio of CRC cells. Furthermore, the in vivo results showed that CDC42SE2 overexpression resulted in lower tumor size in xenograft mice model using stably CDC42SE2-overexpressing CRC cells. Moreover, our study demonstrated that CDC42SE2 can suppress CDC42 and downstream IQGAP3 signaling and thus inhibit the epithelial-mesenchymal transition and invasive potential of CRC cells.In conclusion, CDC42SE2 is a new anti-oncogene of CRC and plays its role in inhibiting epithelial-mesenchymal transition and tumor metastasis by suppressing CDC42 and downstream IQGAP3.