Neddylation: a novel modulator of the tumor microenvironment.

Abstract

Neddylation, a post-translational modification that adds an ubiquitin-like protein NEDD8 to substrate proteins, modulates many important biological processes, including tumorigenesis. The process of protein neddylation is overactivated in multiple human cancers, providing a sound rationale for its targeting as an attractive anticancer therapeutic strategy, as evidence by the development of NEDD8-activating enzyme (NAE) inhibitor MLN4924 (also known as pevonedistat). Neddylation inhibition by MLN4924 exerts significantly anticancer effects mainly by triggering cell apoptosis, senescence and autophagy. Recently, intensive evidences reveal that inhibition of neddylation pathway, in addition to acting on tumor cells, also influences the functions of multiple important components of the tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts (CAFs), cancer-associated endothelial cells (CAEs) and some factors, all of which are crucial for tumorigenesis. Here, we briefly summarize the latest progresses in this field to clarify the roles of neddylation in the TME, thus highlighting the overall anticancer efficacy of neddylaton inhibition.

• Authors: Lisha Zhou, Yanyu Jiang, Qin Luo, Lihui Li, Lijun Jia
• Journal: Molecular cancer (Mol Cancer) Vol. 18 Issue 1 Pg. 77 (04 03 2019) ISSN: 1476-4598 [Electronic] England
• PMID: 30943988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cyclopentanes
• NEDD8 Protein
• NEDD8 protein, human
• Pyrimidines
• pevonedistat

Topics

• Cancer-Associated Fibroblasts (drug effects, metabolism)
• Cell Survival (drug effects)
• Cellular Senescence
• Clinical Trials as Topic
• Cyclopentanes (pharmacology, therapeutic use)
• Humans
• NEDD8 Protein (antagonists & inhibitors, metabolism)
• Neoplasms (drug therapy, metabolism)
• Pyrimidines (pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Tumor Microenvironment (drug effects)