Abstract 4600: Regulation of Wnt/β-catenin signaling by Wnt co-receptor LRP6 in colorectal cancer cells

Abstract

Abstract Mutations of APC and CTNNB1 are two major factors for Wnt/β-catenin signaling over-activation in colorectal cancer, however recent studies indicate that the levels of Wnt/β-catenin signaling in colorectal cancer cells could be modulated on the cell surface. The low-density lipoprotein-related protein 6 (LRP6) is an essential Wnt co-receptor for the Wnt/β-catenin signaling pathway. Herein, we reported that LRP6 expression is up-regulated in colorectal cancer. Moreover, LRP6 silencing significantly reduced Wnt/β-catenin signaling in colorectal cancer HCT116 cells (harboring a CTNNB1 mutation) and DLD-1 cells (harboring an APC mutation) and inhibited cancer cell viability. In addition, treatment of HCT116 cells with Wnt3A resulted in LRP6 phosphorylation and activation of Wnt/β-catenin signaling, which was blocked by LRP6 antagonist Mesd. Finally, we found that salinomycin, a potent small molecule inhibitor of LRP6, suppressed LRP6 expression and phosphorylation, inhibited Wnt/β-catenin signaling in colorectal cancer HCT116 and DLD-1 cells, and repressed cancer cell viability and colony formation within the same concentration range. Together, these results indicate that LRP6 plays an important role in over-activation of Wnt/β-catenin signaling in colorectal cancer cells, and that LRP6 is a potential therapeutic target for colorectal cancer. Citation Format: Yonghe Li, Wenyan Lu, Taj D. King. Regulation of Wnt/β-catenin signaling by Wnt co-receptor LRP6 in colorectal cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4600.