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World J Clin Oncol. Mar 24, 2022; 13(3): 168-185
Published online Mar 24, 2022. doi: 10.5306/wjco.v13.i3.168
Intestinal Wnt in the transition from physiology to oncology
Julia Swoboda, Patrick Mittelsdorf, Yuan Chen, Ralf Weiskirchen, Johannes Stallhofer, Silke Schüle, Nikolaus Gassler
Julia Swoboda, Patrick Mittelsdorf, Yuan Chen, Nikolaus Gassler, Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany
Ralf Weiskirchen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen 52074, Germany
Johannes Stallhofer, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena 07747, Germany
Silke Schüle, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena 07747, Germany
Author contributions: Swoboda J wrote the paper; Mittelsdorf P designed the figures and helped to draft the manuscript; Chen Y, Weiskirchen R, Stallhofer J and Schüle S participated in drafting the article and critically revising it; Gassler N conceived the concept and also contributed to figures and correction.
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Nikolaus Gassler, MA, MD, Professor, Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Am Klinikum 1, Jena 07747, Germany.
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: July 29, 2021
Revised: September 7, 2021
Accepted: February 19, 2022
Article in press: February 19, 2022
Published online: March 24, 2022

Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of stem cells, which can result in dysfunctional epithelial. One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway. It is a highly conserved pathway, with β-catenin, a transcription factor, as target protein. Translocation of β-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripo-tency, proliferation, cell differentiation and regulation of cell death. This review presents a brief overview of the Wnt/β-catenin signaling pathway, the regulatory mechanism of this pathway and its role in intestinal homeostasis. Additionally, this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation. Furthermore, the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.

Keywords: Wnt signaling, Beta-catenin, Intestine, Colorectal cancer, Cell signaling, Intestinal stem cells

Core Tip: Wnt signaling pathway is a key regulator of intestinal stem cells. Mutations in this pathway are frequently found in adenomas and carcinomas of the colorectum. Therefore, it represents a potential target for anticancer therapy. This review sums up the physiological role and the regulatory mechanism of Wnt signaling in the human intestine, and moreover, discusses the central role of the Wnt signaling pathway in intestinal carcinogenesis, the morphological features associated with Wnt hyperactivation and clinical relevance of Wnt in the colorectal carcinoma.