Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [RNA-seq]

ABSTRACT: Activation of the androgen receptor (AR) is the key lineage-specific oncogenic pathway and the primary therapeutic target in prostate cancer. While AR signaling is enabled by the pioneer transcription factor FOXA1, its homologue FOXA2 is specifically expressed in advanced lineage plasticity prostate cancers that have lost the AR signaling axis. However, their roles and utility as a drug target remain incompletely characterized. Here, we show an unexpected collaboration of FOXA1 and FOXA2 in mediating AR-independent cell proliferation in different lineage plasticity cancer subtypes. Conversely, joint loss-of-function or pharmacologic disruption of FOXA1 and FOXA2 leads to the collapse of lineage-specific oncogenic transcription factors followed by cell cycle arrest. In summary, our findings uncover a druggable dependency for AR-positive and -negative prostate cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279872 | GEO | 2025/08/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [ChIP-seq]

Project description:Activation of the androgen receptor (AR) is the key lineage-specific oncogenic pathway and the primary therapeutic target in prostate cancer. While AR signaling is enabled by the pioneer transcription factor FOXA1, its homologue FOXA2 is specifically expressed in advanced lineage plasticity prostate cancers that have lost the AR signaling axis. However, their roles and utility as a drug target remain incompletely characterized. Here, we show an unexpected collaboration of FOXA1 and FOXA2 in mediating AR-independent cell proliferation in different lineage plasticity cancer subtypes. Conversely, joint loss-of-function or pharmacologic disruption of FOXA1 and FOXA2 leads to the collapse of lineage-specific oncogenic transcription factors followed by cell cycle arrest. In summary, our findings uncover a druggable dependency for AR-positive and -negative prostate cancers.

2025-08-30 | GSE281784 | GEO

Identify FOXA2-interacting proteins in NEPC cells

Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.

2025-06-12 | PXD061080 | Pride

Identify FOXA2-interacting proteins in NEPC cells

2025-06-12 | PXD061127 | Pride

FOXA2/AP-1 drives prostate cancer lineage plasticity [ChIP-seq]

Project description:FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.

2024-04-22 | GSE232552 | GEO

FOXA2/AP-1 drives prostate cancer lineage plasticity [RNA-seq]

2024-04-22 | GSE232554 | GEO

FOXA2/AP-1 drives prostate cancer lineage plasticity [PDX ChIP-seq]

2024-04-22 | GSE232553 | GEO

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer

Project description:Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer

| PRJNA1185712 | ENA

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [RNA-seq]

Project description:Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [RNA-seq]

| PRJNA1174995 | ENA

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [ChIP-seq]

Project description:Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output in Prostate Cancer [ChIP-seq]

| PRJNA1185711 | ENA

SOX2 utilizes FOXA1 as a heteromeric transcriptional partner to drive proliferation in therapy-resistant prostate cancer

Project description:Treatment options and diagnostic outlook for men with advanced, therapy resistant prostate cancer (PCa) are extremely poor; this is primarily due to the common lack of durable response to androgen receptor (AR) targeted therapies and phenotypic transdifferentiation into a particularly lethal subtype known as neuroendocrine prostate cancer (NEPC). In this study, we mechanistically determine that SOX2 (a transcription factor originally repressed by AR) physically binds and acts in a concerted manner with FOXA1 (a key AR pioneering cofactor) to regulate a subset of genes which promote cell cycle progression and lineage plasticity in AR-refractory prostate cancers. Our findings assert the SOX2/FOXA1 interaction as an important mediator of resistance to AR-targeted therapy and a driver of NEPC and lineage plasticity; their coordinated action and downstream signaling offers a potential novel therapeutic opportunity in late-stage PCa.

2025-07-25 | GSE303171 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data