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Series GSE65313 Query DataSets for GSE65313
Status Public on Feb 22, 2016
Title Breast Cancer Suppressor Role of RUNX1: Estrogen-dependent Regulation of AXIN1 and b-catenin
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The transcription factor RUNX1 exhibits recurrent loss-of-function mutations in estrogen receptor-positive (ER+) breast cancer (BCa). Its knockdown in vitro decreased AXIN1 expression in estrogen-dependent manner. Consistently, RUNX1 and AXIN1 mRNA levels are strongly correlated in ER+, not ER- tumors. RUNX1 occupies AXIN1’s second intron in living cells, abutting an ERa-binding site. Potentially promoting BCa progression, decreased AXIN1 expression after RUNX1 knockdown associated with upregulation of b-catenin, and this was preventable by AXIN stabilizers. Unlike in colon cancer, however, deregulation of b-catenin in BCa cells affect neither c-Myc, nor CCND1, nor G1/S cell cycle phase transition. Instead, cyclin B1 was decreased and the G2/M checkpoint was compromised as indicated by mitotic slippage in the presence of microtubule disruptors. Thus, combined analysis of the RUNX1 transcriptome, its cistrome, and differential mRNA expression in tumors with wild type versus mutant RUNX1, altogether highlight a role for the RUNX1/AXIN1/b-catenin axis in ER+ BCa. Significance: Three recent exome sequencing studies assigned to RUNX1 a BCa suppressor role. The present study begins to uncover the underlying molecular mechanisms, offers an explanation for the specificity to ER+ tumors, and marks AXIN1 as a therapeutic target for ER+/RUNX1- BCa.
Overall design Examination of RUNX1 binding in MCF7 cells
Contributor(s) Chimge N, Little GH, Baniwal SK, Adisetiyo H, Zhang T, O’Laughlin A, Ulrich P, Liu Z, Martin A, Mhawech-Fauceglia P, Ellis M, Tripathy D, Liang C, Schones DE, Frenkel B
Citation(s) 26916619
Submission date Jan 26, 2015
Last update date May 15, 2019
Contact name Dustin E Schones
Organization name City of Hope
Street address 1500 E Duarte Rd.
City Duarte
State/province CA
ZIP/Postal code 91010
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (3)
GSM1592326 RUNX1 ChIP-seq replicate 1
GSM1592327 RUNX1 ChIP-seq replicate 2
GSM1592328 input control
BioProject PRJNA273658
SRA SRP052837

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Supplementary file Size Download File type/resource
GSE65313_RAW.tar 40.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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