| ISSN |
1007-9327 (print) and 2219-2840 (online) |
| 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/ |
| Copyright |
© The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved. |
| Article Reprints |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
|
| Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
|
| Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
| Website |
http://www.wjgnet.com |
| Category |
Medicine, Research & Experimental |
| Manuscript Type |
Basic Study |
| Article Title |
ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
Xiao-Cheng Tang, Zi-Jian Chen, Chun-Yu Chen, Jun Qiu, Jin-Tuan Huang, Rong-Chang Tan, Wei-Yao Li, Hao Chen and Zu-Li Yang |
| ORCID |
|
| Funding Agency and Grant Number |
| Funding Agency |
Grant Number |
| National Natural Science Foundation of China |
81802322 |
| National Natural Science Foundation of China |
81902949 |
| Natural Science Foundation of Guangdong Province |
2020A1515011362 |
| Natural Science Foundation of Guangdong Province |
2022A1515010262 |
| Science and Technology Program of Guangdong Province |
2022A0505030004 |
|
| Corresponding Author |
Zu-Li Yang, Additional Professor, Chief Physician, Department of General Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People's Republic of China. yangzuli@mail.sysu.edu.cn., Guangzhou 510655, Guangdong Province, China. yangzuli@mail.sysu.edu.cn |
| Key Words |
Biomarker; Chemoresistance; Apoptosis; Intercellular adhesion molecule 2; Tumor microenvironment |
| Core Tip |
Intercellular adhesion molecule 2 (ICAM2) is both a predictive biomarker and a mechanistic mediator of chemoresistance in advanced gastric cancer. Low serum and tissue ICAM2 identify neoadjuvant nonresponders and predict shorter survival. Functionally, ICAM2 loss increases 5-fluorouracil (5-FU) resistance by impairing caspase-dependent apoptosis and remodeling an immunosuppressive, M2-biased macrophage milieu. Mechanistically, ICAM2 loss activates TGF-β/Smad signaling, which upregulates the transcription factor SP1; SP1 then directly pleiotrophin (PTN). Targeting TGF-β suppresses PTN and restores 5-FU sensitivity in preclinical models, positioning the ICAM2/TGF-β/Smad/SP1/PTN axis as a clinically actionable pathway. |
| Publish Date |
2026-01-28 09:23 |
| Citation |
Tang XC, Chen ZJ, Chen CY, Qiu J, Huang JT, Tan RC, Li WY, Chen H, Yang ZL. ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer. World J Gastroenterol 2026; 32(5): 115301 |
| URL |
https://www.wjgnet.com/1007-9327/full/v32/i5/115301.htm |
| DOI |
https://dx.doi.org/10.3748/wjg.v32.i5.115301 |
