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Series GSE132624 Query DataSets for GSE132624
Status Public on Jun 13, 2019
Title MITF controls the TCA cycle to modulate the melanoma hypoxia response
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In response to the dynamic intra-tumor microenvironment, melanoma cells adopt different phenotypic states possessing distinct biological properties associated with differential expression of the microphthalmia-associated transcription factor (MITF). The response to hypoxia, a major microenvironmental cue, is underpinned by expression of hypoxia-inducible transcription factors (HIFs) that reprogram metabolism and promote pro-angiogenic VEGF expression. HIF1 indirectly represses MITF via the transcription factor bHLHE40/DEC1, and MITF can activate HIF1 expression. Although HIF and MITF share a highly related DNA-binding specificity, it is unclear whether they share a subset of target genes. Moreover, the genome-wide impact of hypoxia on melanoma, which genes are direct HIF targets, and whether melanoma cell lines representing different phenotypic states exhibit distinct hypoxic responses is unknown. Here we show, that three different melanoma cell lines exhibit widely different hypoxia responses with only a core 23 genes regulated in common after 12 h in hypoxia. Surprisingly, under hypoxia MITF is transiently up-regulated by HIF1 and co-regulates a subset of HIF targets including VEGFA. Significantly, we also show that MITF represses itself and also regulates SDHB to control the TCA cycle and suppress pseudo-hypoxia. Our results reveal a previously unsuspected role for MITF in metabolism and the network of factors underpinning the hypoxic response in melanoma.
 
Overall design Melanoma cell lines representing 3 phenotypically distinct states were subjected to time-course hypoxia treatment for transcriptomic analysis
 
Contributor(s) Louphrasitthiphol P, Goding CR, Ledaki I
Citation(s) 31207090
Submission date Jun 12, 2019
Last update date Sep 11, 2019
Contact name Pakavarin Louphrasitthiphol
E-mail(s) pakavarin.louphrasitthiphol@ludwig.ox.ac.uk
Phone 01865 617543
Organization name Ludwig Institute for Cancer Research
Department Nuffield Department of Clinical Medicine
Lab Prof. CRGoding
Street address Old Road Campus Research Building (off Roosevelt Drive)
City Oxford
ZIP/Postal code OX3 7DQ
Country United Kingdom
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (36)
GSM3882337 501_t0_R1 (3 phenotypically distinct states dataset)
GSM3882338 501_t0_R2 (3 phenotypically distinct states dataset)
GSM3882339 501_t0_R3 (3 phenotypically distinct states dataset)
Relations
BioProject PRJNA548550
SRA SRP201221

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
GSE132624_edgeR_501mel_DMEM_1_O2_12h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 606.7 Kb (ftp)(http) CSV
GSE132624_edgeR_501mel_DMEM_1_O2_24h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 599.1 Kb (ftp)(http) CSV
GSE132624_edgeR_501mel_DMEM_1_O2_48h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 606.4 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR37_DMEM_1_O2_12h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 545.3 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR37_DMEM_1_O2_24h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 553.8 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR37_DMEM_1_O2_48h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 554.3 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR39_DMEM_1_O2_12h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 559.2 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR39_DMEM_1_O2_24h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 589.9 Kb (ftp)(http) CSV
GSE132624_edgeR_IGR39_DMEM_1_O2_48h_relative_to_0h_QLF-test_filtered_1cpm_3rep.csv.gz 590.9 Kb (ftp)(http) CSV
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