Dataset Information

Proximity labeling proteomics of the androgen receptor reveals Kruppel-Like Factor 4 as a repressor of androgen-dependent genes

ABSTRACT: Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men and is the third cause of cancer mortality. PCa initiation and growth is driven by the androgen receptor (AR). AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. We sought to characterize global AR signalling networks. We performed BioID proximity labeling proteomics in androgen-dependent LAPC4 cells to delineate AR protein interaction networks. We report the identification of 32 AR associated proteins in non-stimulated cells. Strikingly, the AR signalling network increased to 183 and 201 proteins, upon 24h or 72h androgenic stimulation, respectively. Among this group, we identified 215 proteins that were not previously reported as AR interactors. Interestingly, these AR associated proteins were previously reported to be involved in DNA metabolism, RNA processing and RNA polymerase II transcription. Moreover, we identified 44 transcription factors, such as the Krüppel-like factor 4 (KLF4), which was specifically revealed in androgen-stimulated cells. We determined that KLF4 acts as a repressor of AR target genes transcription in PCa cells. Taken together, our data report the largest high-confidence proximity networks for AR in PCa cells.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Lauriane Velot

LAB HEAD: Nicolas Bisson

PROVIDER: PXD011974 | Pride | 2021-03-01

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Ingel20833.raw	Raw
	Ingel20833_150603041159F072376.mzid.gz	Mzid
	Ingel20833_150603041159F072376.mzid_Ingel20833_150603041159_F072376.MGF	Mzid
	Ingel20834.raw	Raw
	Ingel20834F072377.mzid.gz	Mzid

Items per page:

1 - 5 of 108

Publications

Proximity-dependent Mapping of the Androgen Receptor Identifies Kruppel-like Factor 4 as a Functional Partner.

Vélot Lauriane L Lessard Frédéric F Bérubé-Simard Félix-Antoine FA Tav Christophe C Neveu Bertrand B Teyssier Valentine V Boudaoud Imène I Dionne Ugo U Lavoie Noémie N Bilodeau Steve S Pouliot Frédéric F Bisson Nicolas N

Molecular & cellular proteomics : MCP 20210226

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the third cause of cancer mortality. PCa initiation and growth are driven by the androgen receptor (AR). The AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. Here, we report an AR signaling network generated using BioID proximity labeling proteomics in androgen-dependent LAPC4 cells. We identified 31 AR-associated proteins in nonstimulated cells. Strikingly, the AR si ...[more]

PMID: 33640491

Similar Datasets

Project description:The androgen receptor (AR) plays a key role in progression to incurable androgen-ablation resistant prostate cancer (PCA). We have identified three novel AR splice variants lacking the ligand binding domain (designated as AR3, AR4 and AR5) in hormone insensitive PCA cells. AR3, one of the major splice variants expressed in human prostate tissues, is constitutively active and its transcriptional activity is not regulated by androgens or antiandrogens. Immunohistochemistry analysis on tissue microarrays containing 429 human prostate tissue samples shows that AR3 is significantly upregulated during PCA progression and AR3 expression level is correlated with the risk of tumor recurrence after radical prostatectomy. Overexpression of AR3 confers ablation-independent growth of PCA cells while specific knock-down of AR3 expression (without altering AR level) in hormone resistant PCA cells attenuates their growth under androgen-depleted conditions in both cell culture and xenograft models, suggesting an indispensable role of AR3 in ablation-independent growth of PCA cells. Furthermore, AR3 may play a distinct yet essential role in ablation-independent growth through regulating a unique set of genes including AKT1, which are not regulated by the prototype AR. Our data suggest that aberrant expression of AR splice variants may be a novel mechanism underlying ablation-independence during PCA progression and AR3 may serve as a prognostic marker to predict patient outcome in response to hormonal therapy. Given that these novel AR splice variants are not inhibited by currently available anti-androgen drugs, development of new drugs targeting these AR isoforms may potentially be effective for treatment of ablation-resistant PCA. Total RNA was extracted from CWR-R1 and 22Rv1 cells treated with shAR3-1, shARa and the scrambled shRNA control, respectively. Each of CWR-R1 and 22Rv1 cells treated with shAR3-1 was compared with the scrambled shRNA control. The same experiments were performed for the cells treated with shARa.