Whole genome pooled shRNA screen to characterize Raptinal-induced apoptosis in the MIA PaCa-2 cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66423 | GEO | 2018/02/27
REPOSITORIES: GEO
Similar Datasets
Project description:Pancreatic ductal adenocarcinoma, caused by activating mutation in K-Ras, is an aggressive malignancy due to its early invasion and matastasis. Ral GTPases, negatively regulated by RalGAP, are activated downstream of Ras and play a crucial role in development and progression of pancreatic ductal adenocarcinoma. However, the underlying mechanisms remain unclear. We used microarrays to detail the global programme of gene expression underlying the human pancreatic ductal adenocarcinoma cell line, MIA PaCa-2 with RalGAPβ deficiency or not, and identified distinct classes of Ral activation-related mRNA.
2023-04-24 | GSE223382 | GEO
Project description:This a model from the article:
Computational insights on the competing effects of nitric oxide in regulating
apoptosis.
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. PLoS One
2008 May 28;3(5):e2249 18509469
,
Abstract:
Despite the establishment of the important role of nitric oxide (NO) on
apoptosis, a molecular-level understanding of the origin of its dichotomous pro-
and anti-apoptotic effects has been elusive. We propose a new mathematical model
for simulating the effects of nitric oxide (NO) on apoptosis. The new model
integrates mitochondria-dependent apoptotic pathways with NO-related reactions,
to gain insights into the regulatory effect of the reactive NO species N(2)O(3),
non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The
biochemical pathways of apoptosis coupled with NO-related reactions are
described by ordinary differential equations using mass-action kinetics. In the
absence of NO, the model predicts either cell survival or apoptosis (a bistable
behavior) with shifts in the onset time of apoptotic response depending on the
strength of extracellular stimuli. Computations demonstrate that the relative
concentrations of anti- and pro-apoptotic reactive NO species, and their
interplay with glutathione, determine the net anti- or pro-apoptotic effects at
long time points. Interestingly, transient effects on apoptosis are also
observed in these simulations, the duration of which may reach up to hours,
despite the eventual convergence to an anti-apoptotic state. Our computations
point to the importance of precise timing of NO production and external
stimulation in determining the eventual pro- or anti-apoptotic role of NO.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. (2008) - version=1.0
The original CellML model was created by:
Wendy Kang
wkan014@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230064 | BioModels
Project description:This a model from the article:
Computational insights on the competing effects of nitric oxide in regulating
apoptosis.
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. PLoS One
2008 May 28;3(5):e2249 18509469
,
Abstract:
Despite the establishment of the important role of nitric oxide (NO) on
apoptosis, a molecular-level understanding of the origin of its dichotomous pro-
and anti-apoptotic effects has been elusive. We propose a new mathematical model
for simulating the effects of nitric oxide (NO) on apoptosis. The new model
integrates mitochondria-dependent apoptotic pathways with NO-related reactions,
to gain insights into the regulatory effect of the reactive NO species N(2)O(3),
non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The
biochemical pathways of apoptosis coupled with NO-related reactions are
described by ordinary differential equations using mass-action kinetics. In the
absence of NO, the model predicts either cell survival or apoptosis (a bistable
behavior) with shifts in the onset time of apoptotic response depending on the
strength of extracellular stimuli. Computations demonstrate that the relative
concentrations of anti- and pro-apoptotic reactive NO species, and their
interplay with glutathione, determine the net anti- or pro-apoptotic effects at
long time points. Interestingly, transient effects on apoptosis are also
observed in these simulations, the duration of which may reach up to hours,
despite the eventual convergence to an anti-apoptotic state. Our computations
point to the importance of precise timing of NO production and external
stimulation in determining the eventual pro- or anti-apoptotic role of NO.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. (2008) - version=1.0
The original CellML model was created by:
Wendy Kang
wkan014@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230026 | BioModels
Project description: Not available
| S-EPMC4756684 | biostudies-literature
Project description:Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid-like protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and cell death pathways, but its role in apoptosis remained enigmatic. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac/DIABLO as a PARL substrate. In apoptotic cells, Smac/DIABLO is released into the cytosol and promotes caspase activity by inhibiting IAPs. Intramembrane cleavage of Smac/DIABLO by PARL generates an amino terminal IAP-binding motif, which is required for its apoptotic activity. Loss of PARL impairs proteolytic maturation of Smac/DIABLO, which fails to bind XIAP. Smac/DIABLO peptidomimetics, downregulation of XIAP or cytosolic expression of cleaved Smac/DIABLO restores apoptosis in PARL-deficient cells. Our results discover a pro-apoptotic function of PARL and identify PARL-mediated Smac/DIABLO processing and cytochrome c release facilitated by OPA1 dependent cristae remodeling as two independent pro-apoptotic pathways in mitochondria. Please note that these data are overlapping with data uploaded under: PXD004914. Exclusively in this upload, you will find the S277A mutant immunoprecipitations.
2017-03-01 | PXD005712 | Pride
Project description:Small molecule inhibitors of key apoptosis regulators have been developed that bind to anti-apoptotic molecules like BCL-2, leading to release of pro-apoptotic proteins and cell death induction. This study shows that functional analysis of the interplay of apoptosis regulators in precursor B-ALL predicts preclinical in vivo activity of the BCL-2 inhibitor venetoclax and provides a robust assay for upfront identification of leukemias eligible for therapy.
2019-08-06 | GSE123883 | GEO
Project description:To determine the C1GALT1 regulated gene expression profile in MIA PaCa-2 cells.
2017-12-04 | GSE90668 | GEO
Project description:In colorectal cancer, p53 is commonly inactivated, associated with chemo-resistance, and marks the transition from non-invasive to invasive disease. Cancers, including colorectal cancer, are thought to be diseases of aberrant stem cell populations, as stem cells are able to self-renew, making them long-lived enough to acquire mutations necessary to manifest the disease. We have shown that extracts from sweet sorghum stalk components eliminate colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms are unknown. In the present study, CCSC were transfected with short hairpin-RNA against p53 (CCSC p53 shRNA) and treated with sweet sorghum phenolics extracted from different plant components (dermal layer, leaf, seed head and whole plant). While all components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspases 3/7 activity, PARP cleavage, and DNA fragmentation in a p53-dependent and p53-independent fashion, respectively. Further investigations revealed that the anti-proliferative and pro-apoptotic effects were associated with decreases in beta-catenin protein levels, and beta-catenin targets cyclin D1, cMyc, and survivin. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against human colon cancer stem cells are via suppression of Wnt/beta-catenin pro-survival signaling in a p53-dependent (dermal layer) and partial p53-independent (seed head) fashion. LCMS used to identify phenolic compounds associated with extract activity
2014-05-01 | MTBLS69 | MetaboLights
Project description:Non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g. T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/VEGFR inhibitor described here, exerted antiproliferative and pro-apoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g. caspase -2, -3, -7 and -9), but not in the extrinsic (e.g. caspase-8) pathway. Caspase inhibition conferred partial protection against BMS-690514 cytotoxicity, pointing to the involvement of both caspase-dependent and -independent effector mechanisms. Transcriptome analyses revealed the upregulation of pro-apoptotic (e.g. Bim, Puma) and cell cycle inhibitory (e.g. p27Kip1, p57Kip2) factors, as well as the downregulation of anti-apoptotic (e.g. Mcl1), heat shock (e.g. HSP40, HSP70, HSP90) and cell cycle promoting (e.g. cyclins B1, D1 and D3, CDK1, MCM family proteins, PCNA) proteins. BMS-690514-induced death of H1975 cells was modified in a unique fashion by a panel of siRNAs targeting apoptosis modulators. Downregulation of components of the NF-kappaB survival pathway (e.g. p65, Nemo/IKK, TAB2) sensitized cells to BMS-690514, whereas knockdown of pro-apoptotic factors (e.g. Puma, Bax, Bak, caspase-2, etc) and DNA damage-related proteins (e.g. ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC.
2007-07-24 | E-TABM-239 | biostudies-arrayexpress
Project description:Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis, as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain. DU145 cells were treated with ST3-Hel2A-2 or DMSO as a control for 3 hr. Total RNA has been extracted and prepared for hybridization on Affymetrix HG-U133A 2.0 arrays.
2010-12-07 | E-GEOD-25866 | biostudies-arrayexpress