Feng ML, Sun MJ, Xu BY, Liu MY, Zhang HJ, Wu C. Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion, migration, and angiogenesis in colorectal cancer. World J Gastroenterol 2023; 29(24): 3770-3792 [PMID: 37426316 DOI: 10.3748/wjg.v29.i24.3770]
Corresponding Author of This Article
Can Wu, PhD, Associate Research Scientist, Attending Doctor, Department of Endoscopy, The First Hospital Affiliated to China Medical University, No. 155 Nanjing North Street, Shenyang 110000, Liaoning Province, China. wucanydyy@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
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/
Ming-Liang Feng, Ming-Jun Sun, Bo-Yang Xu, Meng-Yuan Liu, Hui-Jing Zhang, Can Wu, Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Feng ML and Sun MJ designed the research study; Feng ML and Wu C performed the research; Zhang HJ and Liu MY contributed new reagents and analytic tools; Feng ML and Xu BY analyzed the data; Feng ML and Wu C wrote the manuscript; and all authors have read and approve the final manuscript.
Supported bythe Natural Science Foundation of Liaoning Province, No. 2023-MS-149.
Institutional review board statement: The study was reviewed and approved by the institutional review board of the First Affiliated Hospital of China Medical University (approval No. 2021-68-2).
Informed consent statement: The informed consent was waived from the patients.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Data can be acquired from the corresponding author.
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: Can Wu, PhD, Associate Research Scientist, Attending Doctor, Department of Endoscopy, The First Hospital Affiliated to China Medical University, No. 155 Nanjing North Street, Shenyang 110000, Liaoning Province, China. wucanydyy@163.com
Received: January 18, 2023 Peer-review started: January 18, 2023 First decision: March 26, 2023 Revised: April 8, 2023 Accepted: May 12, 2023 Article in press: May 12, 2023 Published online: June 28, 2023 Processing time: 160 Days and 19 Hours
Abstract
BACKGROUND
As a novel endogenous anti-angiogenic molecule, vasohibin 1 (VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer (CRC). Knockdown of VASH1 enhanced transforming growth factor-β1 (TGF-β1)/Smad3 pathway activity and type I/III collagen production. Our previous findings suggest that ELL-associated factor 2 (EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3 (STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.
AIM
To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.
METHODS
We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.
RESULTS
Our findings indicated that EAF2 was down-regulated and VASH1 was up-regulated in advanced CRC tissue compared to normal colorectal tissue. Kaplan-Meier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.
CONCLUSION
This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cell-derived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.
Core Tip: Endothelial cell-derived vasohibin 1 (VASH1) can regulate tumor angiogenesis and lymphangiogenesis, and tumor cell-derived VASH1 also has a potential functional role in inhibiting cancer cell proliferation and invasion. Knockdown of VASH1 enhanced transforming growth factor beta 1 (TGF-β)/Smad3 pathway activity and type I/III collagen production. Our previous findings suggest that ELL-associated factor 2 (EAF2) may play a tumor suppressor and protective role in the development and progression of colorectal cancer (CRC) by regulating signal transducer and activator of transcription 3 (STAT3)/TGF-β1 signaling pathway. In this study, we found that EAF2 was down-regulated and VASH1 was up-regulated in advanced CRC tissue compared to normal colorectal tissue by immunohistochemistry and Western blot. And the expression levels of EAF2 and VASH1 were positively correlated in advanced CRC tissue. Furthermore, in vitro cellular mechanism studies suggest that overexpression of EAF2 may inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, thereby attenuating the invasion, migration and angiogenesis of CRC cells. This study provides new ideas and theoretical basis for the development of new diagnostic markers for CRC and the exploration of the mechanism of targeted therapy.
