Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells

Malinen, Marjo; Toropainen, Sari; Jääskeläinen, Tiina; Sahu, Biswajyoti; Jänne, Olli A.; Palvimo, Jorma J.

doi:10.1016/j.mce.2015.07.024

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…Consistent with our findings, the protein abundance and nuclear localization of PIAS1 has been suggested to correlate with patient survival [28]. PIAS1 has also been suggested to promote breast cancer cell apoptosis [29]. Interestingly, in a PIAS1 TMA-based study of primary breast tumors, where correlation with patient survival data were not reported, PIAS1 was found to be increased in abundance in breast tumor-derived tissue [30].…”

Section: Discussionsupporting

confidence: 85%

Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

et al. 2017

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Metastasis is the ultimate cause of breast cancer related mortality. Epithelial-mesenchymal transition (EMT) is thought to play a crucial role in the metastatic potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by which PIAS1 might regulate breast cancer metastasis remain to be elucidated. Using tissue-microarray analysis (TMA), we report that the protein abundance and subcellular localization of PIAS1 correlate with disease specific overall survival of a cohort of breast cancer patients. In mechanistic studies, we find that PIAS1 acts via sumoylation of the transcriptional regulator SnoN to suppress invasive growth of MDA-MB-231 human breast cancer cell-derived organoids. Our studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation pathway in controlling breast cancer metastasis.

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Section: Discussionsupporting

confidence: 85%

Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

et al. 2017

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“…Three replicate experiments for AR ChIP-seq were extracted from a study by Malinen et al . [ 63 ]. The data from these replicates were analyzed to identify the subset of AR-signature genes that have a detectable AR-binding site within their 5 kb promoter regions.…”

Section: Methodsmentioning

confidence: 99%

C1orf64 is a novel androgen receptor target gene and coregulator that interacts with 14-3-3 protein in breast cancer

Naderi

2017

Oncotarget

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This study investigated the network of genes that are co-expressed with androgen receptor (AR) to discover novel AR targets in breast cancer. Bioinformatics analysis of two datasets from breast cancer cell lines resulted in the identification of an AR-gene signature constituted of 98 genes that highly correlated with AR expression. Notably, C1orf64 showed the highest positive correlation with AR across the datasets with a correlation coefficient (CC) of 0.737. In addition, C1orf64 closely correlated with AR expression in primary and metastatic breast tumors and C1orf64 expression was relatively higher in breast tumors with a lower grade and lobular histology. Furthermore, there is a functional interplay between AR and C1orf64 in breast cancer. In this process, AR activation directly represses C1orf64 transcription and C1orf64, in turn, interacts with AR as a corepressor and negatively regulates the AR-mediated induction of prolactin-induced protein (PIP) and AR reporter activity. Moreover, the corepressor effect of C1orf64 results in a reduction of AR binding to PIP promoter. The other aspect of this interplay involves a cross-talk between AR and estrogen receptor (ER) signaling in which C1orf64 silencing intensifies the AR-mediated down-regulation of ER target gene, progesterone receptor. Therefore, the repression of C1orf64 by AR provides an underlying mechanism for the AR inhibitory effects on ER signaling. To elucidate the biochemical mechanisms of C1orf64 function, this study demonstrates that C1orf64 is a phosphothreonine protein that interacts with the chaperone protein 14-3-3. In summary, C1orf64 is a novel AR coregulator and a 14-3-3 binding partner in breast cancer.

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“…In addition to the TF's cognate DNA-binding sites, RNA polymerase II (Pol II) and general transcription machinery, transcriptional regulation requires a number of TF-interacting coregulator proteins, coactivators and corepressors ( 10 , 11 ). Protein inhibitor of activated STAT (PIAS) proteins 1–4 can interact with and coregulate several TFs, including the AR and the NF-κB ( 12 – 15 ). PIAS1 for example can either as an AR coactivator or a corepressor, depending on the AR target gene and it can also influence the distribution of AR on chromatin ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between androgen and pro-inflammatory signaling remodels androgen receptor and NF-κB cistrome to reprogram the prostate cancer cell transcriptome

et al. 2016

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Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells. Co-stimulation of LNCaP cells with androgen and pro-inflammatory cytokine TNFα invoked a transcriptome which was very distinct from that induced by either stimulation alone. The altered transcriptome that included gene programs linked to cell migration and invasiveness was orchestrated by significant remodeling of NF-κB and AR cistrome and enhancer landscape. Although androgen multiplied the NF-κB cistrome and TNFα restrained the AR cistrome, there was no general reciprocal tethering of the AR to the NF-κB on chromatin. Instead, redistribution of FOXA1, PIAS1 and PIAS2 contributed to the exposure of latent NF-κB chromatin-binding sites and masking of AR chromatin-binding sites. Taken together, concomitant androgen and pro-inflammatory signaling significantly remodels especially the NF-κB cistrome, reprogramming the PC cell transcriptome in fashion that may contribute to the progression of PC.

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Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells

Cited by 10 publications

References 37 publications

Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

C1orf64 is a novel androgen receptor target gene and coregulator that interacts with 14-3-3 protein in breast cancer

Crosstalk between androgen and pro-inflammatory signaling remodels androgen receptor and NF-κB cistrome to reprogram the prostate cancer cell transcriptome

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