KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway

Background: Colorectal cancer (CRC) is one of the most common aggressive malignancies. KLHL22 functions as a tumor suppressor, and previous findings have demonstrated that KLHL22 can regulate the development of breast cancer and CRC. However, few studies have investigated the role of KLHL22 in CRC cell epithelial-to-mesenchymal transition (EMT) and proliferation. The current study aimed to detect the role of KLHL22 in CRC cell proliferation and EMT and to elucidate the probable molecular mechanisms through which KLHL22 is involved with these processes. Materials and Methods: Transwell invasion, MTT, immunohistochemistry and Western blotting assays were performed to evaluate the migration, invasion and proliferation abilities of CRC cells, and the levels of active molecules involved in the Wnt/beta-catenin signaling pathway were examined through Western blotting analysis. In addition, the in vivo function of KLHL22 was assessed using a tumor xenograft model. Results: KLHL22 expression was weaker in CRC tissues than in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation in vitro. Furthermore, the regulatory effects of KLHL22 on EMT were partially attributed to the Wnt/beta-catenin signaling pathway. The in vivo results also showed that KLHL22 modulated CRC tumorigenesis. Conclusion: KLHL22 can regulate the activity of GSK-3 beta to influence the level of PI3K, and this regulation promotes EMT inhibition partially through the Wnt/beta-catenin signaling pathway.