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ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer.

Abstract：

:Two opposing clusters of transcription factors (TF) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1. Moreover, signaling through FGFR2, a known risk factor in breast cancer development, augmented these interactions and further repressed ESR1 target gene expression. We therefore show that members of two opposing clusters of risk TFs associated with ESR1-positive and -negative breast cancer can physically interact. We postulate that this interaction forms a toggle between two developmental pathways affected by FGFR2 signaling, possibly offering a junction to exploit therapeutically.Significance: Binding of the transcription factors NFIB and YBX1 to the estrogen receptor can promote an estrogen-independent phenotype that can be reverted by inhibiting FGFR2 signaling. Cancer Res; 78(2); 410-21. ©2017 AACR.

journal_name

Cancer Res

journal_title

Cancer research

authors

Campbell TM,Castro MAA,de Oliveira KG,Ponder BAJ,Meyer KB

doi

10.1158/0008-5472.CAN-17-1153

subject

Has Abstract

pub_date

2018-01-15 00:00:00

pages

410-421

issue

2

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-17-1153

journal_volume

78

pub_type

杂志文章

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