Language
English
Publication Date
3-28-2025
Journal
Science Advances
DOI
10.1126/sciadv.ads6021
PMID
10.1126/sciadv.ads6021
PMCID
PMC11939035
PubMedCentral® Posted Date
3-26-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the expression of 3-phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), two enzymes for serine biosynthesis implicated in brain metastasis. Silencing PHGDH or PSAT1 in metastatic breast cancer cells inhibits their growth in the serine/glycine-limited condition, phenocopying the effects of NAT10 depletion. These findings establish NAT10 as a key regulator of brain metastasis and nominate NAT10 as a target for treating metastasis.
Keywords
Brain Neoplasms, Humans, Animals, Cell Line, Tumor, Cell Proliferation, N-Terminal Acetyltransferase E, Mice, Cell Movement, Female, Phosphoglycerate Dehydrogenase, Transaminases, Gene Expression Regulation, Neoplastic, Breast Neoplasms, Neoplasm Metastasis, N-Terminal Acetyltransferases
Published Open-Access
yes
Recommended Citation
Chen, Jocelyn F; Xu, Peng; Cai, Wesley L; et al., "An In Vivo Screen Identifies NAT10 as a Master Regulator of Brain Metastasis" (2025). Faculty, Staff and Students Publications. 6564.
https://digitalcommons.library.tmc.edu/baylor_docs/6564