Wnt/β-Catenin Signaling Pathway in the Development and Progression of Colorectal Cancer

Abstract

The Wnt/β-catenin signaling pathway is a growth control pathway involved in various biological processes as well as the development and progression of cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. The hyperactivation of Wnt signaling is observed in almost all CRC and plays a crucial role in cancer-related processes such as cancer stem cell (CSC) propagation, angiogenesis, epithelial-mesenchymal transition (EMT), chemoresistance, and metastasis. This review will discuss how the Wnt/β-catenin signaling pathway is involved in the carcinogenesis and progression of CRC and related therapeutic approaches.

Keywords: APC; CRC therapy; Wnt pathway; colorectal carcinogenesis.

Figure 1

Wnt/β-catenin signaling in the target cell. In the absence of Wnt ligands, the free cytoplasmic level of β-catenin is reduced by the activity of the β-catenin destruction complex (Axin, APC, CK1 and GSK3). TCF/LEF together with other molecules act as repressors of gene transcription. The Wnt/β-catenin signaling is activated when Wnt ligands bind to the FZD receptors and the LRP5/6 co-receptors on the target cells, which leads to recruitment of Disheveled (Dvl), causing the relocalization of the destruction complex to the receptor. β-catenin accumulates and then translocates to the nucleus, interacting with TCF/LEF to activate gene transcription. (By Figdraw).