Gene expression signatures in anoikis-resistance of human prostate PC-3 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE100629 | GEO | 2020/06/26
REPOSITORIES: GEO
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Project description:Anoikis resistance or evasion of cell death triggered by cell detachment is a hallmark of cancer that is concurrent with cell survival and metastasis. Phenotypes of anoikis resistant cancer cells have been extensively investigated, however, how exposure to suspension stress may lead to acquisition of a anoikis resistance phenotype has not been previously described in detail. Here we show using a spectrum of ovarian cancer cells, that cycles of suspension stress followed by attached growth, leads to adaptation and acquisition of resistance to cell death in suspension . Comparing the stepwise transcriptomic changes as cells acquire resistance, we find strong transcriptional reprogramming in the population with a majority of differentially expressed genes being downregulated during progressive acquisition of anoikis resistance. Adapted anoikis resistant cells display an enhanced dependency on oxidative phosphorylation and are capable of evasion from T cell-mediated immune surveillance. We find that such acquired anoikis resistance is not genetic. However, transcriptional reprogramming is essential to this process as acquisition of such adaptive anoikis resistance invitro and invivo are both exquisitely sensitive to specific inhibition of transcriptional reprogramming. Our data demonstrate that recovery from the verge of anoikis leads to adaptation that promotes metastasis in ovarian cancer, but can be therapeutically prevented by specific inhibitors to transcriptional reprogramming.
2024-12-01 | GSE241546 | GEO
Project description:Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation.
2019-03-11 | GSE125561 | GEO
Project description:Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation.
2019-03-11 | GSE106592 | GEO
Project description:Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. Several published reports have demonstrated that non-adherent spheres culture is increasingly used as an effective method to enrich and identify stem cells or putative CSCs.In our previous study, we enriched prostate cancer stem cells from PC-3 sphere cells in serum-free suspension culture and characterized their CSCs properties.Thus, we used spheres as a prostate cancer stem cells model to elucidate its metastatic mechanisms. We examined the miRNA expression profiles of PC-3 sphere cells of prostate cancer compared with PC-3 adherent cells by miRNA microarray.
2013-04-01 | E-GEOD-44069 | biostudies-arrayexpress
Project description:Prostate cancer is the leading type of cancer diagnosed and the third leading cause of cancer-related deaths worldwide each year in men. The limitations of the current prostate cancer screening test demands new biomarkers for early diagnosis of prostate cancer metastasis to bone. In this study, we performed a deep proteomic analysis of secreted proteins from the prostate cancer bone metastasis cell line, PC-3, and normal prostate cell line, RWPE-1. Here, we quantified 917 proteins and found 68 highly secreted in PC-3 versus RWPE-1 cells using LC-MS/MS. To characterize the highly secreted proteins in the PC-3 cell line to identify biomarker proteins, the quantifiable proteins were divided into four quantitative categories (Q1-Q4). The KEGG pathways of lysine degradation and osteoclast differentiation were enriched in Q4, the highly secreted group. Transforming growth factor (TGF) beta family proteins related to osteoclast differentiation were identified as key regulators in PC-3 cells. Among the 68 highly secreted proteins, pentraxin, follistatin, and TGF-beta family members were confirmed by immunoblots. In particular, serpin B3, modulated by TGF-beta, was detected and its selective expression and secretion in PC-3 cells was confirmed. In the present study, we suggest that serpin B3 is a novel biomarker candidate for diagnosis of prostate cancer metastasis to the bone.
2017-08-30 | PXD006252 | Pride
Project description:We investigated gene expression profiles of gefitinib-resistant PC-9 (PC-9GR) cells as well as naïve PC-9 cells. The data exhibited marked differences in the expression profiles between them.
2016-12-31 | GSE72197 | GEO
Project description:To investigate the mechanisms underlying castration-resistant prostate cancer (CRPC) development, we used a prostate cancer (PCa) allograft mouse model. In this model, an androgen-dependent (AD) mouse prostate cancer cell line, Myc-CaP, was used. Myc-CaP cells can grow as primary prostate tumors (PPC) in immune competent FVB mice in an AD manner, when host mice are castrated, Myc-CaP allografts shrink (shrunken prostate tumor, S-PC), and later re-grow and become AR-positive CRPC. To compare the gene expression of different stage of PCa, primary cells from PPC, S-PC, and CRPC were isolated and purified. We used RNA-seq to detail the global programme of gene expression underlying castration-resistant prostate cancer (CRPC) development and identified distinct classes of up-regulated or down-regulated genes during this process.
2022-12-15 | GSE208321 | GEO
Project description:BACKGROUND. Human prostate cancer LNCaP and PC-3 cell lines have been extensively used as prostate cancer cell models to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer development, respectively, there is limited information regarding comprehensive gene expression patterns between these two cells lines and relating these cells to prostate cancer progression based on their gene expression. METHODS. Comprehensive gene expression analysis was performed in LNCaP and PC-3 cells. Total RNA was isolated from cultured cells and hybridized to Illumina human Ref-8 version 3 BeadChips representing 24,526 transcripts. Bioinformatics approach was applied to identify genes, their functional roles and interaction networks that are unique in either LNCaP or PC-3 cells. RESULTS. We observed large differences in gene expression between LNCaP and PC-3 cells.Using robust statistical analysis and very high significance criteria to identify tractable number of genes 115 and 188 genes were identified uniquely expressed in LNCaP and PC-3 cells, respectively. Genes uniquely expressed in LNCaP cells contained UDP-glucosyltransferases as a signature for this cell line. This cell line demonstrated upregulation of various metabolic pathways on gene expression level. Talα/β, GATA-1 and c-Myc/Max were identified by in silico analysis as possible transcription factors regulating unique LNCaP genes. PC-3 cells were characterized by cytosceleton-related genes, keratins in particular. Several other well known genes (VEGFC, IL8, TGFβ2 and others) scattered throughout literature were identified and summarized in the discussion. CONCLUSIONS. This study demonstrated that LNCaP and PC-3 cells represent two distinct prostate cancer cell lineages. LNCaP cells retain many prostate cell specific properties, whereas PC-3 cells have acquired more aggressive bone-like characteristics following bone metastasis and show little resemblance to prostate cells. Microarray studies confirmed previously published results and provided more information between these two prostate cancer cell lines. Future studies need to consider their similarities and differences in gene expression between localized and metastasized prostate cancer.
2009-04-27 | GSE13131 | GEO
Project description:PC-9 cells were exposed in vitro to the reversible EGFR inhibitor ZD1839 (gefitinib) and resistant clones were isolated. One of these resistant clones (PC-9 GR4) was then exposed to the irreversible EGFR inhibitor PF00299804 and dual-resistant clones (PC-9 DRs), or those resistant to both ZD1839 and PF00299804, were isolated. In order to compare global genomic changes between PC-9, PC-9 GR, and PC-9 DR cells, we performed a genome-wide SNP analysis.
2009-12-09 | GSE19388 | GEO
Project description:Melanoma tumors are highly heterogeneous, comprising of many cell populations that vary in their potential for growth and invasion. Differential transcription factor expression contributes to these phenotypic traits. BRN2, a member of the POU domain family of transcription factors is thought to play important roles in melanoma invasion and metastasis. However, how BRN2 functions during the metastatic process of melanoma remains largely unknown. We therefore investigated the effects of BRN2 expression in melanoma cells with no or low constitutive expression using a doxycycline-inducible system. Induction of BRN2 expression led to reduced proliferation and partial resistance to an inhibitor of mutated BRAF. Whole genome profiling analysis revealed novel targets and signaling pathway changes related to prevention of cell death induced by detachment from the extracellular matrix, known as anoikis resistance. Further investigation confirmed increased survival of BRN2 expressing cell lines in non-adherent conditions. Functionally, expression of BRN2 promoted induction of c-MET levels as well as increased phosphorylation of STAT3. Treatment with crizotinib, a c-MET inhibitor, decreased cellular viability of BRN2 expressing cells under non-adherent conditions to death by anoikis. These results highlight the importance of a largely overlooked transcription factor in the progression and metastasis of melanoma, and may suggest a strategy to target BRN2 expressing cells resistant to therapy and cell death by anoikis.
2020-02-25 | GSE145806 | GEO