Effect of Trp53 and Rb1 knockout and Myc overexpression on fallopian tube epithelial organoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE255127 | GEO | 2024/05/07
REPOSITORIES: GEO
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Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (Ras mutated)
Crosstalk model of the ERK, Wnt and Akt
signalling pathways with Ras mutation.
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000654.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-08-21 | BIOMD0000000654 | BioModels
Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (PI3K mutated)
Crosstalk model of the ERK, Wnt and Akt
signalling pathways with mutated PI3K.
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000652.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-03-21 | BIOMD0000000652 | BioModels
Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (normal)
Crosstalk model of the ERK, Wnt and Akt
signalling pathways under normal condition.
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000648.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-03-21 | BIOMD0000000648 | BioModels
Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (EGFR overexpression)
Crosstalk model of the ERK, Wnt and Akt
signalling pathways with EGFR overexpression.
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000656.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-08-09 | BIOMD0000000656 | BioModels
Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (PTEN mutation)
Crosstalk model of the ERK, Wnt and Akt
Signalling pathways with PTEN mutation.
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000655.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-08-21 | BIOMD0000000655 | BioModels
Project description:Padala2017- ERK, PI3K/Akt and Wnt signalling
network (bRaf mutated)
Crosstalk model of the ERK, Wnt and Akt
signalling pathways with bRaf mutation
This model is described in the article:
Cancerous perturbations
within the ERK, PI3K/Akt, and Wnt/?-catenin signaling network
constitutively activate inter-pathway positive feedback
loops.
Padala RR, Karnawat R, Viswanathan
SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5):
830-840
Abstract:
Perturbations in molecular signaling pathways are a result
of genetic or epigenetic alterations, which may lead to
malignant transformation of cells. Despite cellular robustness,
specific genetic or epigenetic changes of any gene can trigger
a cascade of failures, which result in the malfunctioning of
cell signaling pathways and lead to cancer phenotypes. The
extent of cellular robustness has a link with the architecture
of the network such as feedback and feedforward loops.
Perturbation in components within feedback loops causes a
transition from a regulated to a persistently activated state
and results in uncontrolled cell growth. This work represents
the mathematical and quantitative modeling of ERK, PI3K/Akt,
and Wnt/?-catenin signaling crosstalk to show the dynamics of
signaling responses during genetic and epigenetic changes in
cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk
networks include both intra and inter-pathway feedback loops
which function in a controlled fashion in a healthy cell. Our
results show that cancerous perturbations of components such as
EGFR, Ras, B-Raf, PTEN, and components of the destruction
complex cause extreme fragility in the network and
constitutively activate inter-pathway positive feedback loops.
We observed that the aberrant signaling response due to the
failure of specific network components is transmitted
throughout the network via crosstalk, generating an additive
effect on cancer growth and proliferation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000653.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2019-03-21 | BIOMD0000000653 | BioModels
Project description:Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multi-layered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.
2022-04-04 | PXD020271 | Pride
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Project description:<p>The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.</p>
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Project description:High-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy. While HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. The goal of this study was to establish the global landscape of HGSC tumor-specific antigens (TSAs) using a mass spectrometry pipeline that interrogates all reading frames of all genomic regions. In 23 HGSC tumors, we identified 113 TSAs. Classic TSA discovery approaches focusing only on mutated exonic sequences would have uncovered only seven of these TSAs. Other mutated TSAs resulted from out-of-frame exonic translation or from non-exonic sequences. The most interesting group of TSAs (n = 94) derived from aberrantly expressed unmutated genomic sequences which are not expressed in normal tissues. These aberrantly expressed TSAs (aeTSAs) derived primarily from non-exonic sequences, in particular intronic (31%) and intergenic (22%). Their expression was regulated at the transcriptional level by variations in gene copy number and DNA methylation. While mutated TSAs were unique to individual tumors, aeTSAs were shared by a large proportion of HGSCs. We conclude that, in view of their number and the fact that they are shared by many tumors, aeTSAs may be the most attractive targets for HGSC immunotherapy.
2020-02-18 | PXD014062 | Pride