Files and links (1)
Published, Version of Record (VoR)CC BY-NC V4.0, Open
Journal article
Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca2+-NFAT signaling
Genes & development, v 32(7-8), pp 497-511
01 Apr 2018
PMID: 29674394
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The metabolite acetyl-coenzyme A (acetyl-CoA) is the required acetyl donor for lysine acetylation and thereby links metabolism, signaling, and epigenetics. Nutrient availability alters acetyl-CoA levels in cancer cells, correlating with changes in global histone acetylation and gene expression. However, the specific molecular mechanisms through which acetyl-CoA production impacts gene expression and its functional roles in promoting malignant phenotypes are poorly understood. Here, using histone H3 Lys27 acetylation (H3K27ac) ChIP-seq (chromatin immunoprecipitation [ChIP] coupled with next-generation sequencing) with normalization to an exogenous reference genome (ChIP-Rx), we found that changes in acetyl-CoA abundance trigger site-specific regulation of H3K27ac, correlating with gene expression as opposed to uniformly modulating this mark at all genes. Genes involved in integrin signaling and cell adhesion were identified as acetyl-CoA-responsive in glioblastoma cells, and we demonstrate that ATP citrate lyase (ACLY)-dependent acetyl-CoA production promotes cell migration and adhesion to the extracellular matrix. Mechanistically, the transcription factor NFAT1 (nuclear factor of activated T cells 1) was found to mediate acetyl-CoA-dependent gene regulation and cell adhesion. This occurs through modulation of Ca2+ signals, triggering NFAT1 nuclear translocation when acetyl-CoA is abundant. The findings of this study thus establish that acetyl-CoA impacts H3K27ac at specific loci, correlating with gene expression, and that expression of cell adhesion genes are driven by acetyl-CoA in part through activation of Ca2+-NFAT signaling.
Metrics
Details
- Title
- Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca2+-NFAT signaling
- Creators
- Joyce V. Lee - Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USACorbett T. Berry - University of PennsylvaniaKarla Kim - University of PennsylvaniaPayel Sen - University of PennsylvaniaTaehyong Kim - University of PennsylvaniaAlessandro Carrer - University of PennsylvaniaSophie Trefely - University of PennsylvaniaSteven Zhao - University of PennsylvaniaSully Fernandez - University of PennsylvaniaLauren E. Barney - University of Massachusetts AmherstAlyssa D. Schwartz - University of Massachusetts AmherstShelly R. Peyton - University of Massachusetts AmherstNathaniel W. Snyder - Drexel UniversityShelley L. Berger - University of PennsylvaniaBruce D. Freedman - University of PennsylvaniaKathryn E. Wellen - University of Pennsylvania
- Publication Details
- Genes & development, v 32(7-8), pp 497-511
- Publisher
- Cold Spring Harbor Lab Press, Publications Dept
- Number of pages
- 15
- Grant note
- Pennsylvania Department of Health Commonwealth Universal Research Enhancement Program (CURE) grant 1DP2CA186573-01 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K22ES026235 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) K12GM081259 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32 GM008515 / National Research Service Award from the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA F31CA189744 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Pew Biomedical Scholar Award Advancing Graduate Studies (AGS) Patel Family Scholar Award 1-18-PDF-144 / American Diabetes Association post-doctoral fellowship K12 GM081259 / Penn-PORT (Penn-Post-doctoral Opportunities in Research and Teaching) Institutional Research and Academic Career Development Award post-doctoral fellowship University of Pennsylvania Pew Charitable Trusts 1451512 / National Science Foundation Graduate Research Fellowship; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000430838600005
- Scopus ID
- 2-s2.0-85045960578
- Other Identifier
- 991019167827304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Developmental Biology
- Genetics & Heredity