Yang Y, Chen WM. RGS4 in gastric cancer: A multifaceted regulator of focal-adhesion-kinase -phosphatidyl-inositol-3-kinase - protein-kinase-B signaling and epithelial-mesenchymal transition beyond tumor progression. World J Gastroenterol 2025; 31(41): 112642 [DOI: 10.3748/wjg.v31.i41.112642]
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/
Nov 7, 2025 (publication date) through Nov 9, 2025
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World Journal of Gastroenterology
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1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Yang Y, Chen WM. RGS4 in gastric cancer: A multifaceted regulator of focal-adhesion-kinase -phosphatidyl-inositol-3-kinase - protein-kinase-B signaling and epithelial-mesenchymal transition beyond tumor progression. World J Gastroenterol 2025; 31(41): 112642 [DOI: 10.3748/wjg.v31.i41.112642]
World J Gastroenterol. Nov 7, 2025; 31(41): 112642 Published online Nov 7, 2025. doi: 10.3748/wjg.v31.i41.112642
RGS4 in gastric cancer: A multifaceted regulator of focal-adhesion-kinase -phosphatidyl-inositol-3-kinase - protein-kinase-B signaling and epithelial-mesenchymal transition beyond tumor progression
Yun Yang, Wen-Ming Chen
Yun Yang, College of Clinical Medicine, Shandong Second Medical University, Weifang 261042, Shandong Province, China
Yun Yang, Wen-Ming Chen, Department of Oncology, Jining No. 1 People’s Hospital, Jining 272011, Shandong Province, China
Author contributions: Yang Y wrote the original draft of the manuscript, and designed the schematic diagram illustrating the mechanism; Chen WM supervised the study and reviewed and edited the manuscript; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant 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: https://creativecommons.org/Licenses/by-nc/4.0/
Received: August 7, 2025 Revised: September 10, 2025 Accepted: September 28, 2025 Published online: November 7, 2025 Processing time: 92 Days and 7 Hours
Abstract
Chen et al demonstrated that regulator of G protein signaling (RGS) 4 promotes gastric cancer (GC) progression by activating the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and inducing epithelial-mesenchymal transition. Although their multilevel approach integrating clinical data, functional assays, and xenograft models demonstrated a key role for RGS4 in GC pathogenesis, several limitations should be considered. The mechanism of the RGS4-focal adhesion kinase interaction remains unclear, specifically whether it involves direct binding or intermediaries. The clinical analysis of 90 patients lacks stratification by GC subtypes or immune features, potentially limiting generalizability. Furthermore, fully validating RGS4’s oncogenic role requires additional studies, including functional assays in chemotherapy-resistant and metastatic cell lines, metastasis models including orthotopic implantation and tail vein injection, and comparison with other RGS family members. Addressing these via targeted mechanistic studies and expanded clinical validation could strengthen RGS4’s potential as a therapeutic target in GC.
Core Tip: Chen et al provided compelling multilevel evidence that regulator of G-protein signaling 4 drives gastric cancer progression through focal adhesion kinase/phosphoinositide 3-kinase/protein kinase B activation and epithelial-mesenchymal transition, combining clinical correlation with functional validation. Although further mechanistic studies and expanded clinical cohorts would strengthen the findings, this work establishes G-protein signaling 4 as a promising therapeutic target worthy of deeper investigation.
