Project description:This SuperSeries is composed of the following subset Series: GSE30622: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [Expression Array] GSE30623: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [ChIP_seq, DHS_seq] Refer to individual Series
Project description:We report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing. Examination of AR, FoxA1, GR, H3K4me2 binding sites and DHS sites in parental and FoxA1 depleted LNCaP-1F5 cells.
Project description:The aim of this study is to identify the LSD1 target genes in metastatic androgen independent prostate cancer Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.
Project description:The aim of this study is to identify the LSD1 target genes in metastatic androgen independent prostate cancer Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.
Project description:Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13. In summary, by combining proteomic and genomic approaches we reveal subclasses of AR transcriptional complexes, differentiating normal AR behavior from the oncogenic state. In this process, the expression of AR interactors has key roles by reprogramming the AR cistrome and interactome in a genomic location-specific manner.
Project description:We report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing.
Project description:We report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing.
