Open Access Review

Overcoming MTDH and MTDH-SND1 complex: driver and potential therapeutic target of cancer

by Hao Shen a,b,c ,  Jiayu Ding a,b,c ,  Jiaying Ji a,b ,  Binjian Jiang a,b ,  Xiao Wang a,b,c,*  and  Peng Yang a,b,c,* orcid
a
State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
b
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
c
Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China
*
Author to whom correspondence should be addressed.
CI  2023, 29; 3(1), 29; https://doi.org/10.58567/ci03010004
Received: 26 September 2023 / Accepted: 5 December 2023 / Published Online: 11 December 2023
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Abstract

Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Keywords: MTDH; SND1; Protein-Protein interaction; RNA binding protein; Cancer;
Copyright: © 2023 by Shen, Ding, Ji, Jiang, Wang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.