Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by Transcriptionally Activating DSCC1

Sep 21, 2026

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Gastric cancer (GC) ranks as a leading cause of cancer deaths globally, yet the molecular drivers of GC proliferation and metastasis remain insufficiently defined. This study identifies transcription factor Early 2 Factor 4 (E2F4) as a promoter of GC cell proliferation, migration, and invasion through transcriptional activation of DNA Replication and Sister Chromatid Cohesion 1 (DSCC1). Bioinformatics and transcription factor analyses connect E2F4 to DSCC1 regulation, while functional assays confirm enhanced malignancy in vitro and in vivo. Knockdown and overexpression experiments verify transcriptional control, and ChIP-qPCR plus dual luciferase reporter assays validate DSCC1 promoter binding sites, supporting the E2F4-DSCC1 axis as a potential therapeutic target.

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CategoryResearch & Report

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Abstract

Introduction

Ivyspring International Publisher InternationalJournal of Biological Sciences 2024; 20(12): 4978-4998. doi: 10.7150/ijbs.99590 Research Paper Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1 Shantanu Baral1, 2, 3, 4, Yantao Yu4, 6, Qiannan Sun2, 4, Mingrui Jiang1, 2, 3, 4, Ruiqi Li4, 5, Yifan Cheng4, 5, Arawker Mubeen Hussein3, Youquan Shi4, Yongjun Jiang4, Dong Tang2, Sen Wang7, 􀀍, Daorong Wang1, 2, 3, 4, 5, 6, 􀀍 1. Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, P. R. China. 2. Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, P. R. China. 3. General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, Jiangsu, 225001, P. R. China. 4. Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, Jiangsu, 225001, P. R. China. 5. Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, Jiangsu, 225001, P. R. China. 6. The Yangzhou School of Clinical Medicine of Dalian Medical University. Yangzhou, Jiangsu, 225001, P. R. China. 7. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China. 􀀍 Corresponding authors: Daorong Wang, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, P. R. China. [wdaorong666@sina.com](wdaorong666@sina.com); Sen Wang, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, [P. R. China. wangsen1992@hotmail.com](P. R. China. wangsen1992@hotmail.com)[ ](P. R. China. wangsen1992@hotmail.com)© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions. Received: 2024.06.13; Accepted: 2024.09.08; Published: 2024.09.16 Abstract Gastric cancer (GC) ranks as the fifth most common cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4’s role in enhancing GC cell malignancy in vitro and in vivo. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression. Keywords: Gastric Cancer; DNA Replication and Sister Chromatid Cohesion 1; Early 2 Factor 4; transcription; Proliferation Introduction Gastric cancer (GC) is a profoundly deadly disease on a global scale, standing as the fifth most commonly detected cancer and the fourth leading contributor to cancer-related mortality internationally [1] . In recent times, advancements in high-throughput and genomic technologies have enabled the study of gastric cancers at the molecular level. The availability of molecular profiling data has significantly aided in pinpointing potential gene driver alterations in GC, including gene mutations, chromosomal changes, alterations in transcription patterns, and irregularities in epigenetic modifications[2-4] . Therefore, comprehending the process of GC metastasis and pinpointing molecular markers and therapeutic targets associated with metastas

FAQs

What role does E2F4 play in gastric cancer cells?

E2F4 promotes gastric cancer cell proliferation, migration, and invasion by transcriptionally activating DSCC1 expression.

How was the E2F4–DSCC1 regulatory relationship validated?

Bioinformatics and transcription factor analyses identified E2F4 as a regulator of DSCC1, and ChIP-qPCR plus dual luciferase reporter assays validated E2F4 binding sites on the DSCC1 promoter.

What experimental evidence supports E2F4’s effect on cancer malignancy?

Functional assays showed that manipulating E2F4 enhances GC malignancy in vitro and in vivo, and knockdown/overexpression experiments demonstrated positive transcriptional regulation of DSCC1.

Sep 21, 2026

Uploaded by Levi