Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Abstract

Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/β-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of β-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). Objective Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. Methods Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. Results Wnt signaling pathways include: Wnt/β-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. Conclusion The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

Sequential Accumulation of ‘Driver’ Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids

“…Finally, Ade CIN TSK organoids had a significant increase of ACLY and β-catenin. These results confirm previous findings that Wnt/β-catenin pathway activation occurs during colorectal cancer development [ 38 , 39 ]; based on prior studies in human colon cancer cell lines [ 11 , 21 ], upregulation of H 2 S generation may be a potential contributing factor to this process, although the effect of H 2 S biosynthesis inhibitors has not been assessed in the current set of experiments. Interestingly, prior studies have implicated the role of the Wnt/β-catenin pathway in the upregulation of CSE in several human colon cancer cell lines [ 40 ]; whether this mechanism is operative in the current system remains to be further investigated, but there appears to be a correlation: both CSE upregulation and the induction of various Wnt/β-catenin pathway components were found to be most pronounced in the same organoids: AT, Ade CIN TS and Ade CIN TSK ( Figure 1 and Figure 3 ).…”

Microcystin‑leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/β‑catenin pathway

“…Previous studies have demonstrated that the PI3K/Akt and Wnt/β-catenin signaling pathways are closely associated with the occurrence and development of CRC ( 16 , 17 ). Activation of the PI3K/Akt and Wnt/β-catenin signaling pathways can promote CRC cell proliferation ( 18 , 19 ).…”

The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer

“…To combat such unregulated cell growth, the influence of FOXM1 inhibitor needed to be deciphered. Firstly, an MTT assay was conducted in HCT 116 cells by treating with sequential doses of thiostrepton (5,10,15,20,25,30,40,50,60, 70, 80, 90, 100µM) for 24hrs. It was revealed that with increasing doses, the viability of HCT 116 cells kept on decreasing (Fig.…”

“…β-catenin, an effector component of this pathway, is gaining prominence as a molecular marker of cancer. Therefore, understanding the functionality of this pathway is indispensable for developing therapies for colon cancer 5,6 .…”

“…Therefore, understanding the functionality of this pathway is indispensable for developing therapies for colon cancer 5,6 .…”