The Roles of Gelsolin in the Regulation of Wnt Signaling in Colorectal Cancer
Session type: Poster / e-Poster / Silent Theatre session
Wnt signaling has been shown to be involved in embryonic development and is the driver of several diseases, including cancer such gastric and colon cancer. The deregulation of the canonical Wnt/β-catenin signaling can contribute to carcinogenesis via various mechanisms, such as promoting epithelial mesenchymal transition (EMT), invasion and metastasis. Although the non-canonical Wnt signaling has been reported to be involved in cytoskeletal regulation, the interactions between the canonical Wnt/β-catenin signaling pathway and cytoskeletal components are not well understood. Gelsolin is a member of the actin-binding proteins, which are involved in the regulation of actin dynamics through the severing and capping of actin filaments. In cancer, gelsolin promotes tumor progression by enhancing cellular migration, invasion and scattering through the modulating the phosphoinositide-3-kinase/Akt signaling and the activation of urokinase plasminogen activator signaling cascade. The expression of gelsolin was also reported to be altered in the different stages of cancer. The downregulation at early-stages, and subsequent re-expression of gelsolin at advanced stages were observed in cancers including urothelial carcinoma, lung and oral cancer, suggesting the significance of gelsolin in contributing to the aggressiveness of cancer We have previously reported that in colorectal cancer, gelsolin increases cellular invasiveness, correlating with high expression at the invasive front of primary tumours and liver metastases. Interestingly, other groups have reported nuclear β-catenin (indicative of activated Wnt signaling) to be upregulated at the invasive front of colorectal tumors.
We investigated the interactions between gelsolin and Wnt/β-catenin signaling in cancer cells. Using gelsolin overexpression and knockdown models, we found that increased levels of gelsolin enhanced Wnt/β-catenin signaling, whilst gelsolin knockdown reduced Wnt/β-catenin transcriptional activity. We also observed that Wnt-induced migration and changes in cell morphology are affected by gelsolin levels. We postulate that gelsolin may regulate Wnt signaling by affecting the activities of the modulators of the Wnt/β-catenin pathway.