Kunz EM, Schoeller III RJ, Carroll JP, Lucke-Wold B. Translational implications of the MAZ/UHRF1/ECRG4 axis in metastatic colorectal carcinoma. World J Gastrointest Oncol 2026; 18(6): 116858 [DOI: 10.4251/wjgo.v18.i6.116858]
Corresponding Author of This Article
Eric Michael Kunz, Doctorate Student, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, United States. ekunz005@med.fiu.edu
Research Domain of This Article
Gastroenterology & Hepatology
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editorial
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Kunz EM, Schoeller III RJ, Carroll JP, Lucke-Wold B. Translational implications of the MAZ/UHRF1/ECRG4 axis in metastatic colorectal carcinoma. World J Gastrointest Oncol 2026; 18(6): 116858 [DOI: 10.4251/wjgo.v18.i6.116858]
World J Gastrointest Oncol. Jun 15, 2026; 18(6): 116858 Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.116858
Translational implications of the MAZ/UHRF1/ECRG4 axis in metastatic colorectal carcinoma
Eric Michael Kunz, Russell James Schoeller III, Joseph Patrick Carroll, Brandon Lucke-Wold
Eric Michael Kunz, Russell James Schoeller III, Joseph Patrick Carroll, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, United States
Brandon Lucke-Wold, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL 32608, United States
Author contributions: Kunz EM and Schoeller III RJ designed the overall concept and outline of the manuscript; Kunz EM and Lucke-Wold B contributed to the writing, editing the manuscript, and review of literature; Schoeller III RJ and Carroll JP contributed to the discussion and design of the manuscript; Kunz EM, Schoeller III RJ, Carroll JP, and Lucke-Wold B contributed to this paper, read and approved the final version of the manuscript to be published.
AI contribution statement: Grammarly and ChatGPT were used for language polishing and writing assistance for this manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Eric Michael Kunz, Doctorate Student, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, United States. ekunz005@med.fiu.edu
Received: November 24, 2025 Revised: December 21, 2025 Accepted: January 6, 2026 Published online: June 15, 2026 Processing time: 199 Days and 12.8 Hours
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide, mainly due to its high potential for metastasis and limited long-term survival despite modern treatments. The recent study by Mao et al published in World Journal of Gastrointestinal Oncology, reveals a new oncogenic signaling pathway involving Myc-associated zinc finger protein (MAZ), ubiquitin-like with PHD and RING finger domains 1 (UHRF1), and esophageal cancer-related gene 4 (ECRG4). This study details the function of the MAZ/URF1/ECRG4 axis. MAZ functions as a transcriptional activator of UHRF1, an epigenetic regulator that maintains DNA methylation and silences tumor suppressor genes such as ECRG4. Loss of ECRG4 expression promotes epithelial – mesenchymal transition, invasion, and metastasis in CRC. Inhibiting MAZ or UHRF1 restores ECRG4 expression and reduces metastatic behaviors. These findings connect transcriptional activation with epigenetic silencing, revealing a complex mechanism that drives CRC progression. From a therapeutic perspective, targeting MAZ or UHRF1 – or restoring ECRG4 expression – could offer a new epigenetic strategy to reduce metastasis. Overall, this study identifies the MAZ/UHRF1/ECRG4 pathway as a key regulator of CRC spread and emphasizes its potential as a biomarker and therapeutic target in advanced disease.
Core Tip: This manuscript identifies a novel metastatic signaling cascade in colorectal cancer in which Myc-associated zinc finger protein (MAZ) transcriptionally activates the epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (UHRF1), leading to hypermethylation and silencing of the tumor suppressor esophageal cancer-related gene 4 (ECRG4). This MAZ/UHRF1/ECRG4 axis drives epithelial – mesenchymal transition, invasion, and metastasis. Targeting MAZ or UHRF1 – or restoring ECRG4 expression – may offer a promising epigenetic therapeutic strategy for metastatic colorectal carcinoma.
