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Title: The essential role of PBX1, a stem cell reprogramming factor, in ovarian cancer chemoresistance      
dateReleased:
07-25-2016
description:
Elucidating the pathogenesis of chemoresistance is fundamental for developing more effective interventions that will improve the clinical outcome of neoplastic diseases such as ovarian cancer. Here, we report the upregulation of PBX1, a stem cell reprogramming factor, in recurrent ovarian carcinomas. Moreover, high levels of PBX1 expression are correlated with a shorter survival rate among post-chemotherapy ovarian cancer patients. Ectopic expression of PBX1 promotes cancer stem cell-like phenotypes, including increased side population and ALDH activity, enhanced tumorigenicity at a low cell density, and increased resistance to platinum-based therapy. Silencing PBX1 in platinum-resistant cell lines that overexpress PBX1 sensitizes cells to platinum treatment and reduces their “stemness”. Analysis of previously reported genome-wide chromatin immunoprecipitation data shows that PBX1 binds directly to promoters of genes involved in stem cell maintenance and tissue injury response. We confirmed direct regulation of STAT3 by PBX1, and demonstrated that the PBX1 binding motif located on the STAT3 promoter participates in positive transcriptional regulation of STAT3. Furthermore, a STAT3/JAK2 inhibitor potently sensitizes platinum-resistant cells to carboplatin and suppresses their growth in vivo. These findings establish PBX1 as an upstream regulator of key pathways in stem cell and tissue damage response and highlight the potential of targeting the PBX1/STAT3 axis to overcome chemoresistance in human cancers. Determine gene expression changes after knockdown of PBX1 protein in an ovarian cancer cell line (OVCAR3)
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-84755
refinement:
raw
alternateIdentifiers:
84755
keywords:
functional genomics
dateModified:
07-30-2016
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-MEXP-1173
name:
Illumina HumanWG-6 v3.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-84755/E-GEOD-84755.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-84755/E-GEOD-84755.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE84755
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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