Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ATAC-seq)

ABSTRACT: The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting resistance to AR-targeted therapies. By examining the chromatin landscape of AR positive prostate cancer cells following exposure to the AR inhibitor enzalutamide, we have identified a novel regulator of cell plasticity, homeobox transcription factor SIX2, whose motif is enriched in accessible regions post-treatment. Our investigation demonstrates that depletion of SIX2 in androgen-independent PC-3 prostate cancer cells is sufficient to induce a switch from a stem-like to an epithelial state, leading to the reduction of key cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects are mediated through downregulation of Wnt/β-catenin signalling pathway and subsequent reduced nuclear localization of β-catenin. Collectively, our findings provide compelling evidence that depletion of SIX2 may represent a promising strategy for overcoming cell plasticity mechanisms driving AR resistance in prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235955 | GEO | 2024/03/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (RNA-seq)

Project description:The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting resistance to AR-targeted therapies. By examining the chromatin landscape of AR positive prostate cancer cells following exposure to the AR inhibitor enzalutamide, we have identified a novel regulator of cell plasticity, homeobox transcription factor SIX2, whose motif is enriched in accessible regions post-treatment. Our investigation demonstrates that depletion of SIX2 in androgen-independent PC-3 prostate cancer cells is sufficient to induce a switch from a stem-like to an epithelial state, leading to the reduction of key cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects are mediated through downregulation of Wnt/β-catenin signalling pathway and subsequent reduced nuclear localization of β-catenin. Collectively, our findings provide compelling evidence that depletion of SIX2 may represent a promising strategy for overcoming cell plasticity mechanisms driving AR resistance in prostate cancer.

2024-03-19 | GSE235957 | GEO

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ChIP-seq)

2024-03-19 | GSE235956 | GEO

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer

Project description:SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer

| PRJNA988079 | ENA

Inhibition of Androgen Receptor and β-catenin activity in prostate cancer

Project description:Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective new approach to treating prostate cancer. Here we provide proof-of-concept that a small molecule inhibitor of nuclear β-catenin activity (called C3) can inhibit both the AR and β-catenin signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both β-catenin/TCF and β-catenin/AR protein interaction, reflecting the fact that TCF and AR have overlapping binding sites on β-catenin. Given that AR interacts with, and is transcriptionally regulated by β-catenin, C3 treatment also resulted in decreased occupancy of β-catenin on the AR promoter and diminished AR and AR/β-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and β-catenin cofactor, CARM1, providing new insight into the unrecognized function of β-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model, and blocked renewal of bicalutamide-resistant sphere forming cells, indicating the therapeutic potential of this approach. Compare and contrast the expression profile of prostate cancer cells treated with a Wnt inhibitor (C3) with respect to β-catenin and AR knockdown (all samples in duplicates).

2014-01-23 | E-GEOD-49295 | biostudies-arrayexpress

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ChIP-seq)

Project description:SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ChIP-seq)

| PRJNA988085 | ENA

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ATAC-seq)

Project description:SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (ATAC-seq)

| PRJNA988086 | ENA

SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (RNA-seq)

Project description:SIX2 promotes cell plasticity via Wnt/beta-catenin signalling in androgen receptor independent prostate cancer (RNA-seq)

| PRJNA988089 | ENA

Inhibition of Androgen Receptor and β-catenin activity in prostate cancer

2014-01-23 | GSE49295 | GEO

Transcription profiling of human prostate cancer cell lines after androgen depletion and AR knock-down

Project description:Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.

2007-05-04 | E-SMDB-4028 | biostudies-arrayexpress

Transcriptional profiles induced by either androgen depletion or androgen receptor knockdown

2007-08-08 | E-GEOD-7585 | biostudies-arrayexpress