Zhang JJ, Cao CX, Wan LL, Zhang W, Liu ZJ, Wang JL, Guo Q, Tang H. Forkhead Box q1 promotes invasion and metastasis in colorectal cancer by activating the epidermal growth factor receptor pathway. World J Gastroenterol 2022; 28(17): 1781-1797 [PMID: 35633908 DOI: 10.3748/wjg.v28.i17.1781]
Corresponding Author of This Article
Hui Tang, PhD, Professor, Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China. htang1122@aliyun.com
Research Domain of This Article
Research & Experimental Medicine
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/
Jin-Jin Zhang, Chang-Xiong Cao, Li-Lan Wan, Wen Zhang, Zhong-Jiang Liu, Jin-Li Wang, Qiang Guo, Hui Tang, Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China
Jin-Jin Zhang, Chang-Xiong Cao, Li-Lan Wan, Wen Zhang, Zhong-Jiang Liu, Jin-Li Wang, Qiang Guo, Hui Tang, Department of Medical Faculty, Kunming University of Science and Technology, Kunming 650504, Yunnan Province, China
Jin-Jin Zhang, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan Province, China
Author contributions: Zhang JJ and Cao CX contributed equally to this work; Tang H and Guo Q designed the project; Cao CX and Zhang JJ analyzed data and wrote the manuscript; Zhang JJ and Wan LL performed qRT-PCR, Elisa, and Western blotting; Zhang W and Wang JL carried out migration assay; Liu ZJ and Tang H analyzed colorectal tissue microarray and survival data; all authors participated in critical revision of the manuscript and approved the final manuscript.
Supported byNational Natural Science Foundation of China, No. 81502556; and Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province, No. 2X2019-01-02.
Institutional review board statement: Our research does not involve humans and animals.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: No additional data are available.
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: Hui Tang, PhD, Professor, Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China. htang1122@aliyun.com
Received: October 18, 2021 Peer-review started: October 18, 2021 First decision: December 12, 2021 Revised: December 31, 2021 Accepted: March 27, 2022 Article in press: March 27, 2022 Published online: May 7, 2022 Processing time: 192 Days and 21.7 Hours
ARTICLE HIGHLIGHTS
Research background
Invasion and metastasis play important roles in tumorigenesis, resulting in the death of most colorectal cancer (CRC) patients. Forkhead Box q1 (FOXQ1) is a well-established oncogene in multiple tumors, including CRC. However, the role and mechanism of how FOXQ1 promotes tumorigenesis in CRC by activating the heparin-binding epidermal growth factor (HB-EGF)/epidermal growth factor receptor (EGFR) pathway remain largely unknown.
Research motivation
Our study aims to elucidate the critical role of FOXQ1 and HB-EGF/EGFR pathways in CRC, and to provide theoretical support for the clinical application of targeted FOXQ1 in the treatment of CRC.
Research objectives
To determine the role of FOXQ1-induced invasion and metastasis, which are related to activating the HB-EGF/EGFR pathway, and to explore the mechanism by which FOXQ1 promotes tumorigenesis by activating the HB-EGF/EGFR pathway in CRC.
Research methods
We analyzed the correlation between FOXQ1 and the HB-EGF/EGFR pathway by constructing FOXQ1 knockdown cells, tissue microarray, cell function experiments, quantitative real-time polymerase chain reaction (qRT–PCR), flow cytometry, ELISA, western blot, and the Gene Expression Profiling Interactive Analysis (GEPIA) website.
Research results
GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate. PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways. Knockdown of FOXQ1 suppressed the expression of HB-EGF and led to a decrease in EGFR and its downstream genes AKT, RAF, KRAS expression levels. After knockdown of FOXQ1 in CRC cell lines, cell proliferation, migration, and invasion were attenuated. Adding HB-EGF restored the migration and invasion ability of CRC, but the cell proliferation ability was not restored. Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.
Research conclusions
FOXQ1 promotes the invasion and metastasis of CRC by activating the HB-EGF/EGFR pathway.
Research perspectives
In this study, our results indicated that FOXQ1 and HB-EGF may be potential biomarkers to improve the accuracy of CRC diagnosis and treatment.
