Targeting N‐myristoyltransferase1 inhibits prostate cancer progression
Abstract
N‐myristoyltransferase (NMT) facilitates co/post‐translational myristoylation of several oncogenic proteins, regulating their functions in tumor progression. Overexpression of N‐myristoyltransferase (NMT), which has been shown to be upregulated in a variety of cancers, is associated with androgen independent prostate cancer cells. We demonstrate that genetically ablation of NMT1 inhibited proliferation of prostate cancer cells, tumor growth, and suppressed myristoylation profile of prostate cancer cells. Screening a panel of myristoyl‐CoA analogs against purified human NMT1 protein lead to identifying the B13/LCL4 as an inhibitor for NMT1. B13/LCL4 significantly supressed prostate cancer cell proliferation, migration, and invasion by cell cycle arrest, and inhibited the growth of prostate xenograft tumors with minimal pathological effect on major organs in vivo. Structure activity relationship based optimization of B13 led to LCL204, which showed better inhibitory properties twoards NMT1. We demonstrate that targeting protein myristoylation is a potential therapeutic approach to inhibit prostate tumor progression.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2018
- Source ID
- 10.1096/fasebj.2018.32.1_supplement.804.40
Entities
People
- Alicja Bielawska
- Houjian Cai
- Omar Awad Alsaidan
- Qianjin Li
- Sung Jin Kim
Organizations
- Medical University of South Carolina
- National Institutes of Health
- United States Department of Defense
- University of Georgia