Wnt Signaling in the Gastrointestinal Tract in Health and Disease

Abstract

Wnt signaling involves multiple pathways that contribute to organ development, cell fate, inflammation, and normal stem cell renewal and maintenance. Although the homeostasis of stem cells in the gastrointestinal (GI) tract highly depends on the Wnt signaling pathway, this regulation is impaired in cancers and in aging. Overactive (uncontrolled) Wnt signaling can induce GI epithelial cancers such as colon and gastric cancer. Overactive Wnt signaling can also contribute to the initiation and progression of gastrointestinal stromal tumor, which is the most common human sarcoma occurring in the walls of the digestive organs, mainly the stomach and small intestine. Wnt expression is positively associated not only with the progression of oncogenesis but also with resistance to chemotherapy and radiotherapy. Of note, recent reports show that decreased Wnt signaling is related to intestinal stem cell aging and that overactivated Wnt signaling leads to gastric pacemaker stem cell aging in tunica muscularis. These findings indicate that Wnt signaling has different crucial aspects of cell fate determination with age in GI tunica mucosa and muscularis. In this review, we summarize the most recent advances in our understanding of Wnt signaling pathways and their role in regulating key aspects during development, carcinogenesis, inflammation, and aging, with the ultimate goal of identifying novel therapies.

Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics

“…According to pre-clinical and clinical findings, stimulation of the Wnt/β-catenin signaling cascade has been linked to disease pathogenesis, including carcinogenesis. The Wnt/β-catenin signaling pathway is aberrantly stimulated due to mutations in its constituent parts, which promote the migration and invasion of malignancy by increasing the expression of primary targets (c-myc and cyclin D1) that are governed by this pathway and are responsible for cellular growth and programmed cell death [4,5]. A link between cytoplasm and nucleus can be made via β-catenin, which is situated downstream of the Wnt/β-catenin signaling pathway.…”