Cong L, Tong S, Xu YJ, Zhang DY, Zhang XM, Yu H. Metastasis-associated colon cancer 1 drives pancreatic cancer via p53/Notch signaling. World J Gastrointest Oncol 2026; 18(5): 117323 [DOI: 10.4251/wjgo.v18.i5.117323]
Corresponding Author of This Article
Hong Yu, PhD, Department of Pathology, Taizhou People’s Hospital Affiliated to Dalin Medical University, No. 366 Taihu Road, Medical High-tech Zone, Taizhou 225300, Jiangsu Province, China. yuhong@njmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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/
World J Gastrointest Oncol. May 15, 2026; 18(5): 117323 Published online May 15, 2026. doi: 10.4251/wjgo.v18.i5.117323
Metastasis-associated colon cancer 1 drives pancreatic cancer via p53/Notch signaling
Lin Cong, Si Tong, Yu-Jie Xu, De-Yu Zhang, Xiu-Mei Zhang, Hong Yu
Lin Cong, Xiu-Mei Zhang, Department of Pathology, Xinghua People’s Hospital Affiliated to Yangzhou University, Xinghua 225700, Jiangsu Province, China
Si Tong, Department of Ultrasound, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
Yu-Jie Xu, Department of Pathology, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huai’an 2230001, Jiangsu Province, China
De-Yu Zhang, Department of Gastroenterology, Changhai Hospital, Shanghai 200000, China
Hong Yu, Department of Pathology, Taizhou People’s Hospital Affiliated to Dalin Medical University, Taizhou 225300, Jiangsu Province, China
Co-corresponding authors: Xiu-Mei Zhang and Hong Yu.
Author contributions: Cong L and Tong S drafted the manuscript; Cong L, Tong S, and Xu YJ contributed equally to this work, conceived and designed the study, conducted the bioinformatics and statistical analyses; Cong L, Tong S, Xu YJ, and Zhang DY performed the experiments and collected the data; Zhang DY contributed to clinical sample collection and interpretation of clinical data; Zhang XM and Yu H supervised the study and provided critical intellectual input, critically revised the manuscript for important intellectual content as co-corresponding authors; all authors reviewed and approved the final version of the manuscript.
Supported by Project Foundation of Taizhou School of Clinical Medicine, Nanjing Medical University, No. TZKY20220205.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Changhai Hospital, No. CHEC2020-173.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding authors upon reasonable request. Publicly available datasets were obtained from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, cBioPortal, TIMER2.0, and CancerSEA databases.
Corresponding author: Hong Yu, PhD, Department of Pathology, Taizhou People’s Hospital Affiliated to Dalin Medical University, No. 366 Taihu Road, Medical High-tech Zone, Taizhou 225300, Jiangsu Province, China. yuhong@njmu.edu.cn
Received: December 8, 2025 Revised: December 29, 2025 Accepted: February 11, 2026 Published online: May 15, 2026 Processing time: 161 Days and 2.8 Hours
Abstract
BACKGROUND
Metastasis-associated colon cancer 1 (MACC1) is known to promote tumor growth and metastasis in several solid malignancies. However, its expression profile, clinical relevance, and underlying mechanisms in pancreatic cancer (PC) remain incompletely defined.
AIM
To systematically evaluate the multiomics characteristics and clinical significance of MACC1 across cancers and to investigate its biological functions and molecular mechanisms in PC.
METHODS
MACC1 expression, DNA methylation, copy number changes, and genetic alterations were analyzed across The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, cBioPortal, TIMER2.0, CancerSEA, and single-cell datasets. The diagnostic and prognostic value of MACC1 was assessed using Cox models, Kaplan-Meier analysis, and receiver operating characteristic curves. Functional studies were performed by silencing or overexpressing MACC1 in PANC-1 cell and ASPC-1 cell. Cell proliferation, colony formation, migration, invasion, and apoptosis were evaluated. Enriched pathways were screened using gene set enrichment analyses and confirmed by western blot.
RESULTS
MACC1 was significantly upregulated in PC at both mRNA and protein levels in public datasets and our local cohort. High MACC1 expression was linked to advanced stage, poor differentiation, and worse survival. Multiomics analysis showed that MACC1 alterations were common across cancers and were associated with copy number gain and promoter hypomethylation. Functional assays demonstrated that MACC1 enhanced pancreatic tumor proliferation, colony formation, migration, and invasion while reducing apoptosis. Gene set enrichment analyses, dual luciferase gene assay and western blot confirmed that MACC1 activated p53-related and Notch-related signaling in PC cells.
CONCLUSION
MACC1 is a clinically relevant oncogene in PC. Its overexpression promotes aggressive tumor behavior through activation of p53 and Notch pathways. These findings support MACC1 as a potential diagnostic marker and therapeutic target in PC.
Core Tip: Metastasis-associated colon cancer 1 (MACC1) is strongly upregulated in pancreatic cancer (PC) and shows consistent alterations across multiomics datasets. In this study, we combined pan-cancer bioinformatic profiling with functional experiments to clarify its role in PC. Silencing MACC1 suppressed proliferation, migration, invasion, and increased apoptosis, while overexpression produced the opposite effects. We also confirmed that MACC1 activates both p53 and Notch signaling. These findings show that MACC1 is not only a useful diagnostic and prognostic marker but also a potential therapeutic target in PC.
