We find significant evidence of the OVOL, AP1, STAT1, STAT3, and NFKB1 TFs having important roles in MET. We prioritize known gene/drug targets for follow-up in the clinic, and show that the AP1/MYC TF pair is a strong candidate for intervention. Overall design: Examination of the effects of OVOL1 and OVOL2 overexpression common to prostate cancer and breast cancer models.
A bioinformatics approach reveals novel interactions of the OVOL transcription factors in the regulation of epithelial - mesenchymal cell reprogramming and cancer progression.
No sample metadata fields
View SamplesAndrogen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. Surprisingly little is known of AR binding sites and collaborating transcription factors in the human genome. Here we have identified the DNA sequence motifs that are significantly enriched within the authentic 90 AR target regions found on chromosomes 21 and 22 in human prostate cancer cells by combining chromatin immunoprecipitation for AR with chromosome-scale tiled oligonucleotide microarrays. By integrating the DNA sequence motif data with the gene expression profiles from human prostate cancers we identified the transcription factors that recognize each of these motifs. These factors form complexes with AR, bind to specific AR target regions and govern androgen-dependent transcription. Together with AR these collaborating transcription factors form a regulatory network that directs prostate cancer growth and survival and identify potential new opportunities for therapeutic intervention.
A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth.
No sample metadata fields
View SamplesAnalysis of the transcriptome of mouse models of prostate cancer to assemble a mouse prostate cancer interactome.
Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
Treatment
View SamplesAn integrative analysis of this compendium of proteomic alterations and transcriptomic data was performed revealing only 48-64% concordance between protein and transcript levels. Importantly, differential proteomic alterations between metastatic and clinically localized prostate cancer that mapped concordantly to gene transcripts served as predictors of clinical outcome in prostate cancer as well as other solid tumors.
Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression.
No sample metadata fields
View SamplesDissemination of cancer stem cells (CSCs) serves as the basis of metastasis. Recently, we demonstrated that circulating prostate cancer (PCa) targets the hematopoietic stem cell (HSCs) niche in marrow during dissemination. Once in the niche, disseminated tumor cells (DTCs) may remain dormant for extended periods. As the major function of the HSC niche is to maintain stem cell functions, we hypothesized that the niche regulates CSC activities of DTCs. We show that DTCs recovered from marrow were significantly enriched for a CSC phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche. The data demonstrate that the niche plays a significant role in maintaining tumor-initiating PCa in marrow and suggests a functional relationship between CSCs and dormancy. Understanding how the marrow niche regulates the conversion of DTCs to CSCs is critical for the development of therapeutics specifically targeting skeletal bone metastasis and dormancy.
The marrow niche controls the cancer stem cell phenotype of disseminated prostate cancer.
Specimen part
View SamplesCDk4/6 inhibitor activates RB and represses RB/E2F target genes
RB Loss Promotes Prostate Cancer Metastasis.
Cell line, Treatment
View SamplesCDk4/6 inhibitor activates RB and represses RB/E2F target genes
RB Loss Promotes Prostate Cancer Metastasis.
Cell line, Treatment
View SamplesAndrogen receptor (AR) signaling is a distinctive feature of prostate cancer (PC) and represents the major therapeutic target for the treatment of metastatic disease. Though highly effective, AR antagonism has the potential to generate tumors that bypass a functional requirement for AR activity. We show here that a phenotypic shift has occurred in metastatic PCs with the emer-gence of a double-negative AR-null neuroendocrine-null phenotype that is notable for MAPK and FGF pathway activity. To identify mechanisms capable of sustaining PC survival, we gener-ated a model system designated AR program-independent prostate cancer (APIPC) which re-sists AR-targeted therapeutics, lacks neuroendocrine features, expresses high levels of FGF8 and the ID1 oncogene, and activates MAPK signaling. Pharmacological blockade of MAPK or FGF signaling inhibited APIPC tumor growth, supporting FGF/MAPK as a therapeutic avenue for treating AR-null PC. Overall design: RNA sequencing of human prostate tumor cell lines using the Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.
Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling.
Sex, Specimen part, Cell line, Subject
View SamplesPatients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese subjects undergoing bariatric surgery and then used for the mRNA expression analyses. Overall design: mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500.
Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance.
Age, Specimen part, Subject
View SamplesAccumulating evidences suggest that sex affects lung development. During the fetal period, male lung maturation is delayed compared with female and surfactant production appears earlier in female than in male fetal lungs.
Gene expression profile of androgen modulated genes in the murine fetal developing lung.
Specimen part, Disease
View Samples