Malek KK, Kumar B, Ahmad R, Singh A, Basson MD. Focal adhesion kinase: A promising regulator of colitis-associated healing. World J Gastroenterol 2025; 31(33): 105466 [PMID: 40933464 DOI: 10.3748/wjg.v31.i33.105466]
Corresponding Author of This Article
Marc D Basson, MD, PhD, College of Medicine, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, United States. mbasson@neomed.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Sep 7, 2025; 31(33): 105466 Published online Sep 7, 2025. doi: 10.3748/wjg.v31.i33.105466
Focal adhesion kinase: A promising regulator of colitis-associated healing
Kaitlyn Kaye Malek, Balawant Kumar, Rizwan Ahmad, Amar Singh, Marc D Basson
Kaitlyn Kaye Malek, Marc D Basson, College of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, United States
Balawant Kumar, Rizwan Ahmad, Amar Singh, Department of Medicine, University of Kansas Medical Center, Kansas City, MO 66160, United States
Amar Singh, Department of Research, Kansas City VA Medical Center, Kansas City, MO 64128, United States
Co-corresponding authors: Amar Singh and Marc D Basson.
Author contributions: Singh A and Basson MD conceptualized the paper and made equal contributions as co-corresponding authors; Kumar B, Ahmad R, Singh A, and Basson MD supervised the research; all authors contributed to the methodology, investigation, writing the original draft, revisions and edits, and have read and approved the final manuscript.
Conflict-of-interest statement: Dr. Basson reports a patent “Use of small molecule FAK activators to promote mucosal healing”, 2024/0024555A1 issued.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marc D Basson, MD, PhD, College of Medicine, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, United States. mbasson@neomed.edu
Received: January 23, 2025 Revised: June 2, 2025 Accepted: August 15, 2025 Published online: September 7, 2025 Processing time: 221 Days and 12.5 Hours
Abstract
Although the etiology of inflammatory bowel disease (IBD) remains unclear, compromised epithelial barrier integrity is believed to promote susceptibility to IBD and be associated with disease severity, suggesting that improving gut barrier integrity may palliate or treat IBD. Such a notion gets support from the clinical findings that mucosal healing in IBD patients is associated with improved prognosis, and reduced risk of relapse or colitis-associated cancer. It therefore becomes critical to understand the intracellular signals that regulate mucosal healing and gut barrier integrity. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that critically modulates epithelial cell growth and mobility and has been associated with carcinogenesis. However, studies also suggest that FAK activation may promote mucosal healing under conditions of colitis, which should reduce the risk of colitis-associated cancer. These findings highlight a potentially transformative role for FAK in the context of IBD. Understanding the molecular mechanisms by which FAK influences gut barrier repair and mucosal integrity could offer novel therapeutic avenues for treating IBD and preventing its long-term complications. This review focuses on the potential role of FAK in promoting colitis-associated mucosal healing and the underlying molecular mechanisms driving these processes, offering critical insights into IBD pathogenesis and therapy.
Core Tip: Focal adhesion kinase (FAK) plays a critical role in gastrointestinal mucosal healing via various key cellular processes. Small molecule FAK activators, such as ZINC40099027 or analogs, selectively enhance the activity of FAK to promote epithelial cell migration and wound closure. Therefore, ZINC40099027 and similar agents demonstrate promise in treating gastrointestinal mucosal injuries, such as ulcers or inflammatory bowel disease. Their two-fold approach in perpetuating repair mechanisms while minimizing oncogenic pathogenesis offers a therapeutic solution that is a safer, long-term treatment option for complex mucosal injuries.
