EMAIL THIS PAGE TO A FRIEND

BMC cancer

YB-1 regulates Sox2 to coordinately sustain stemness and tumorigenic properties in a phenotypically distinct subset of breast cancer cells.


PMID 24885403

Abstract

Sox2, a transcription factor and an embryonic stem cell marker, has been implicated in the pathogenesis of breast cancer (BC). YB-1 is another transcription factor that has been shown to promote stemness in BC cells. Western blotting, quantitative PCR, and siRNAs were used to query the regulatory relationships between YB-1, Sox2, and their downstream targets. Chromatin immunoprecipitation was used to detect YB-1 interactions at the Sox2 promoter. Mammosphere and soft agar assays were used to assess the phenotypic consequences of YB-1 knockdown. Here, we report that YB-1 regulates Sox2. YB-1 was found to bind to the SOX2 promoter and down-regulate its expression in MCF7 and ZR751. The regulatory interaction between YB-1 and Sox2 was drastically different between the two phenotypically distinct cell subsets, purified based on their differential response to a Sox2 reporter. They are referred to as the reporter unresponsive (RU) cells and the reporter responsive (RR) cells. Upon siRNA knockdown of YB-1, RU cells showed an increase in Sox2 expression but no change in Sox2 reporter activity; in contrast, RR cells exhibited increased expression and reporter activity of Sox2. Correlating with these findings, YB-1 knockdown induced a differential response in the expression of genes known to be regulated by both Sox2 and YB-1 (e.g. CCND1 and ITGA6). For instance, in response to YB-1 knockdown, CCND1 and ITGA6 expression were decreased or unchanged in RU cells but paradoxically increased in RR cells. Compared to RU cells, RR cells were significantly more resistant to the suppression of mammosphere formation due to YB-1 knockdown. Importantly, mammospheres derived from parental MCF7 cells treated with YB-1 siRNA knockdown exhibited higher expression levels of SOX2 and its downstream targets. To conclude, in a subset of BC cells, namely RR cells, YB-1 regulates Sox2 to coordinately maintain stemness and tumorigenic properties.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

AV34395
Anti-NSEP1 (AB2) antibody produced in rabbit, affinity isolated antibody
SAB2701800
Anti-sox2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
S9072 Anti-SOX2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
AV38232
Anti-SOX2 antibody produced in rabbit, IgG fraction of antiserum
SAB3500363
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2104660
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody
SAB4300669
Anti-SOX2 antibody produced in rabbit, affinity isolated antibody
SAB2701973
Anti-SOX2 antibody produced in rabbit
SAB2701974
Anti-SOX2 antibody produced in rabbit
SAB2103958
Anti-SOX2, (N-terminal) antibody produced in rabbit, affinity isolated antibody
HPA002131
Anti-VCL antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Y0271 Anti-YB-1 (N-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB2103783
Anti-YBX1 antibody produced in rabbit, affinity isolated antibody
HPA040304
Anti-YBX1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
I3769 Insulin-like Growth Factor-I human, IGF-I, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
L9908
LY-294,002 hydrochloride, solid, ≥98% (HPLC)
C19H17NO3 · HCl
S1451
Monoclonal Anti-Sox2 antibody produced in mouse, ~1.0 mg/mL, clone SOX2-6, purified immunoglobulin, buffered aqueous solution
SAB5300177
Monoclonal Anti-SOX2 antibody produced in mouse, clone 10F10, ascites fluid
SAB5300369 Monoclonal Anti-SOX2 antibody produced in mouse, clone 10F10C9, ascites fluid
SAB1404522
Monoclonal Anti-VCL antibody produced in mouse, clone 3F8-1D4, purified immunoglobulin, buffered aqueous solution