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Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [microarray]

ABSTRACT: Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [microarray]

PROVIDER: PRJNA490187 | ENA |

REPOSITORIES: ENA

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Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression

Project description:Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression

| PRJNA490185 | ENA

Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [RNA-Seq]

Project description:Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [RNA-Seq]

| PRJNA490188 | ENA

Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [microarray]

Project description:our study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-β signaling and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.

2018-11-01 | GSE119758 | GEO

Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression [RNA-Seq]

2018-11-01 | GSE119757 | GEO

Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression.

Project description:Prostate cancer (PC) progressed to castration resistance (CRPC) is a fatal disease. CRPC tumors develop resistance to new-generation antiandrogen enzalutamide through lineage plasticity, characterized by epithelial-mesenchymal transition (EMT) and a basal-like phenotype. FOXA1 is a transcription factor essential for epithelial lineage differentiation. Here, we demonstrate that FOXA1 loss leads to remarkable upregulation of transforming growth factor beta 3 (TGFB3), which encodes a ligand of the TGF-β pathway. Mechanistically, this is due to genomic occupancy of FOXA1 on an upstream enhancer of the TGFB3 gene to directly inhibit its transcription. Functionally, FOXA1 downregulation induces TGF-β signaling, EMT, and cell motility, which is effectively blocked by the TGF-β receptor I inhibitor galunisertib (LY2157299). Tissue microarray analysis confirmed reduced levels of FOXA1 protein and a concordant increase in TGF-β signaling, indicated by SMAD2 phosphorylation, in CRPC as compared with primary tumors. Importantly, combinatorial LY2157299 treatment sensitized PC cells to enzalutamide, leading to synergistic effects in inhibiting cell invasion in vitro and xenograft CRPC tumor growth and metastasis in vivo. Therefore, our study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-β signaling, and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.

| S-EPMC6355239 | biostudies-literature

FOXA1 inhibits prostate cancer hypoxia program through transcriptional repression of HIF1A

Project description:We and others have previously shown FOXA1 is frequently mutated or downregulated in castration resistant prostate cancer (CRPC). Here we report a novel role for transcription factor FOXA1 in directly repressing HIF1A expression in prostate cancer cells. FOXA1 knockdown induced the expression of HIF1A and hypoxia signature genes, which were reduced by concomitant HIF1A knockdown or treatment with HIF1A inhibitor KC7F2. Thus, our data suggest FOXA1 loss induces aberrant hypoxia signaling and tumor progression in part via HIF1A.

2022-08-29 | GSE195571 | GEO

Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-01 | GSE119759 | GEO

FOXA1 suppresses cancer immunity independent of DNA binding

Project description:FOXA1 suppresses cancer immunity independent of DNA binding

| PRJNA596242 | ENA

Redirecting the pioneering function of FOXA1 with covalent small molecules

Project description:Pioneer transcription factors (TFs) exhibit a special ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. Here, we report electrophilic small molecules that stereoselectively and site-specifically bind the pioneer TF, FOXA1, at a cysteine (C258) within the forkhead DNA-binding domain. We show that these covalent ligands react with FOXA1 in a DNA-dependent manner and rapidly remodel its pioneer activity in prostate cancer cells reflected in redistribution of FOXA1 binding across the genome and directionally correlated changes in chromatin accessibility. Motif analysis supports a mechanism where the covalent ligands relax the canonical DNA binding preference of FOXA1 by strengthening interactions with suboptimal ancillary sequences in predicted proximity to C258. Our findings reveal a striking plasticity underpinning the pioneering function of FOXA1 that can be controlled by small molecules.

2024-09-05 | PXD050685 | Pride

FoxA1 inhibits androgen receptor expression and suppresses prostate cancer metastasis [LNCaP, ChIP-seq]

Project description:FoxA1 has been shown critical for prostate development and prostate-specific gene expression regulation. In addition to its well-established role as an AR pioneering factor,several studies have recently revealed significant AR binding events in prostate cancer cells with FoxA1 knockdown. Furthermore, the role of FoxA1 itself in prostate cancer has not been carefully examined. Thus, it is important to understand the role of FoxA1 in prostate cancer and how it interacts with AR signaling. To address these questions, we generated LNCaP cells with stable FoxA1 knockdown. We performed AR/FoxA1 ChIP-seq and microarray analysis of these cells. ChIP_Seq examination of AR and FoxA1 binding sites in LNCaP shCtrl and shFoxA1 cells

2014-06-02 | E-GEOD-37345 | biostudies-arrayexpress

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