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Series GSE55615 Query DataSets for GSE55615
Status Public on Nov 26, 2014
Title Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. HIF1A is a major regulator of this process but activation of HIF1A under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of Hypoxia Inducible Factor 1A (HIF1A) transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.
Overall design In an attempt to identify the ARRB1 cistrome in prostate cancer cells, C4-2 prostate cancer cells expressing endogenous levels of ARRB1 were used to ChIP for ARRB1, p300 (previously shown to interact with ARRB1within transcriptional complexes), RNA PolII and histone markers H3K4me1 and H4K4me3 (markers for enhancer and promoter regions, respectively). Cells were untreated and cultured in FBS supplemented with 10%FBS. In parallel, C4-2 cells stably expressing a nuclear form of ARRB1 (nucARRB1) were also used to ChIP the same complexes under the same conditions. Finally, human prostate tissue was used to ChIP for ARRB1 and histone markers.
Contributor(s) Zecchini V, Stark R, Russell R
Citation(s) 24837709
Submission date Mar 05, 2014
Last update date May 15, 2019
Contact name Chandra Chilamakuri
Organization name Cancer Research UK Cambridge Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (13)
GSM1340252 parental C4-2(endogenous ARRB1)_ARRB1 ChIP
GSM1340253 nucARRB1 C4-2(high nuclear ARRB1)_ARRB1 ChIP
GSM1340254 nucARRB1 C4-2(high nuclear ARRB1)_p300 ChIP
This SubSeries is part of SuperSeries:
GSE55616 ARRB1 regulates prostate cancer cell metabolism
BioProject PRJNA240221
SRA SRP039441

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55615_RAW.tar 11.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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