Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2022; 28(29): 3753-3766
Published online Aug 7, 2022. doi: 10.3748/wjg.v28.i29.3753
Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer
Eid Alshammari, Ying-Xue Zhang, Zhe Yang
Eid Alshammari, Ying-Xue Zhang, Department of Biochemistry, Microbiology, and Immunology, Wayne State University, Detroit, MI 48201, United States
Zhe Yang, Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, United States
Author contributions: Alshammari E performed the majority of the writing, prepared the figures and tables; Zhang YX provided the input in writing the paper; Yang Z coordinated the writing of the paper and performed writing.
Conflict-of-interest statement: There are no conflicts of interest to report.
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: Zhe Yang, PhD, Associate Professor, Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, United States. zyang@med.wayne.edu
Received: January 18, 2022
Peer-review started: January 18, 2022
First decision: April 11, 2022
Revised: April 24, 2022
Accepted: July 5, 2022
Article in press: July 5, 2022
Published online: August 7, 2022
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases. Understanding the molecular pathogenesis and the underlying mechanisms involved in the initiation, maintenance, and progression of PDAC is an urgent need, which may lead to the development of novel therapeutic strategies against this deadly cancer. Here, we review the role of SET and MYND domain-containing protein 2 (SMYD2) in initiating and maintaining PDAC development through methylating multiple tumor suppressors and oncogenic proteins. Given the broad substrate specificity of SMYD2 and its involvement in diverse oncogenic signaling pathways in many other cancers, the mechanistic extrapolation of SMYD2 from these cancers to PDAC may allow for developing new hypotheses about the mechanisms driving PDAC tumor growth and metastasis, supporting a proposition that targeting SMYD2 could be a powerful strategy for the prevention and treatment of PDAC.

Keywords: Pancreatic ductal adenocarcinoma, Protein lysine methyltransferase, Histone/non-histone methylation, Oncogenic signaling pathways, Methyltransferase inhibitors

Core Tip: The broad substrate specificity of SET and MYND domain-containing protein 2 (SMYD2) and its involvement in diverse oncogenic signaling pathways in numerous cancers have provided a wealth of information that could be extrapolated to the pancreatic ductal adenocarcinoma (PDAC) research field to expand our understanding of SMYD2 in PDAC development. This review not only discusses the known roles of SMYD2 in PDAC initiation and progression, but also aims to capitalize on a rich body of knowledge with respect to SMYD2’s involvement in various signaling cascades to develop new hypotheses about the mechanisms of driving PDAC tumor growth and metastasis.