Role of PTEN in B-ALL
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA650503 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To elucidate the dependence of B-ALL cells on PTEN we analysed the transcriptional changes upon inducible Pten KO in BCR-ABL1 transformed pre-B cells.
2020-10-13 | GSE155618 | GEO
Project description:Faratian2009 - Role of PTEN in Trastuzumab
resistance
This model is described in the article:
Systems biology
reveals new strategies for personalizing cancer medicine and
confirms the role of PTEN in resistance to trastuzumab.
Faratian D, Goltsov A, Lebedeva G,
Sorokin A, Moodie S, Mullen P, Kay C, Um IH, Langdon S, Goryanin
I, Harrison DJ.
Cancer Res. 2009 Aug; 69(16):
6713-6720
Abstract:
Resistance to targeted cancer therapies such as trastuzumab
is a frequent clinical problem not solely because of
insufficient expression of HER2 receptor but also because of
the overriding activation states of cell signaling pathways.
Systems biology approaches lend themselves to rapid in silico
testing of factors, which may confer resistance to targeted
therapies. Inthis study, we aimed to develop a new kinetic
model that could be interrogated to predict resistance to
receptor tyrosine kinase (RTK) inhibitor therapies and directly
test predictions in vitro and in clinical samples. The new
mathematical model included RTK inhibitor antibody binding,
HER2/HER3 dimerization and inhibition, AKT/mitogen-activated
protein kinase cross-talk, and the regulatory properties of
PTEN. The model was parameterized using quantitative
phosphoprotein expression data from cancer cell lines using
reverse-phase protein microarrays. Quantitative PTEN protein
expression was found to be the key determinant of resistance to
anti-HER2 therapy in silico, which was predictive of unseen
experiments in vitro using the PTEN inhibitor bp(V). When
measured in cancer cell lines, PTEN expression predicts
sensitivity to anti-HER2 therapy; furthermore, this
quantitative measurement is more predictive of response
(relative risk, 3.0; 95% confidence interval, 1.6-5.5; P <
0.0001) than other pathway components taken in isolation and
when tested by multivariate analysis in a cohort of 122 breast
cancers treated with trastuzumab. For the first time, a systems
biology approach has successfully been used to stratify
patients for personalized therapy in cancer and is further
compelling evidence that PTEN, appropriately measured in the
clinical setting, refines clinical decision making in patients
treated with anti-HER2 therapies.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000424.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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.
2024-09-02 | BIOMD0000000424 | BioModels
Project description:Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN. Thus, 293T cells were transiently transfected with plasmid encoding Flag-tagged PTEN along with empty vector, followed by affinity purification using an anti-Flag antibody, and the bound proteins were analyzed by liquid chromatography with tandem mass spectrometry (LC−MS/MS). Here we identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN.
2020-04-22 | PXD017983 | Pride
Project description:MicroRNAs are post-transcriptional regulators of gene expression, disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment, explains mechanisms related to cancer progression and pro-vides a potential target of modern therapies. Here we show how tumor hypoxia modifies the miRNA pattern in renal cancer focusing on the dysregulation PTEN being a major tumor suppressor for its regulation of others key suppressors. Methods comprised the CRSPR/Cas9 mediated PTEN knockout in Renca kidney cancer cell line and global miRNA expression analysis in both in vivo and in vitro (in normoxic and hypoxic conditions). The results were validated on human cancer models with distinct PTEN status. The increase in miR210-3p in hypoxia was universal, however, the hypoxia-induced decrease in PTEN was associated with an increase in miR-221-3p, the loss of PTEN affected differently the response to hypoxia by decreasing miR-10b-3-5p and increasing miR-206-3p. In turn, Complete loss of PTEN induces miR-155-5p, miR-100-5p. Upregulation of miR342-3p in knockout PTEN occurred in the context of whole tumor microenvironment. Thus effective identification of miRNA patterns in cancers must consider the specificity of the tumor microenvi-ronment together with the mutations of key suppressors.
2022-05-10 | GSE197301 | GEO
Project description:Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in its phosphatase-independent manner, and identify262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. Especially, the exon-2b exclusion of GOLGA2 contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors, Brefeldin A and Golgicide A. Given that many cancers lack PTEN expression, our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers.
2018-10-18 | PXD009681 | Pride
Project description:PTEN is one of the most frequently mutated tumor suppressor genes, its loss has been reported in multiple tumor types and is associated with a poor outcome. PTEN-L, as a secreted isoform of PTEN, with the ability to enter cells and inhibit tumor cell growth via inhibiting AKT mediated cell proliferation. However, the distinct effect of PTEN-L on PTEN-expression or PTEN-loss tumor cells is not known yet. Here, we identified PTEN-L treatment facilitate E0771-PTEN-null tumor cells, but not PTEN-wide-type tumor cells lung outgrowth. RNA-seq and Western blot analysis suggest PTEN-L stimulation induced PTEN-null tumor cells dormancy, namely, upregulation of dormancy markers p16 and p27, cell cycle arrest, reduced cell proliferation and chemotherapy drugs resistance. Further study suggested PTEN-L mediated p38 signaling activation play the major role for PTEN-null tumor cell dormancy. The p38 inhibitor, SB202190 significantly reversed the PTEN-L induced PTEN-null tumor cells dormancy and outgrowth in lungs. Further investigation indicated the dormant PTEN-null tumor cells could escape from immunosurveillance and thus outgrowth in lungs, as PTEN-L did not promote PTEN-null tumor cells outgrowth in lung of SCID mice. Therefore, we propose that PTEN-L protects PTEN-null tumor cells from immune attack during lung metastasis via activating dormancy related pathways. This study identified PTEN-L as an activator of PTEN-loss tumor cells dormancy, which enables the efficient seeding and outgrowth of tumor cells in metastatic niches. Overall, we highlight PTEN expression status decides the outcome of PTEN-L mediated anti-tumor therapy.
2024-05-17 | GSE246600 | GEO
Project description:extracellular PTEN treatment did not affect the growth of PTEN knockout B16-F10 cells cultured in vitro. , To investigate whether extracellular PTEN act on the tumor microenvironment to exert a tumor-suppressive role in vivo，molecular changes caused by PTEN treatment inside the B16-F10-PTEN tumors were monitored by RNA sequencing.
2024-07-24 | GSE249142 | GEO
Project description:The PTEN tumor suppressor controls cell death and survival by regulating functions of various molecular targets. Whilst the role of PTEN lipid-phosphatase activity on PtdIns(3,4,5)P3 and inhibition of PI3K pathway is well characterized, the biological relevance of PTEN protein-phosphatase activity remains undefined. Using knock-in (KI) mice harbouring cancer-associated and functionally relevant missense mutations, we show that although loss of PTEN lipid-phosphatase function cooperates with oncogenic PI3K to promote rapid mammary tumorigenesis, the additional loss of PTEN protein-phosphatase activity triggered an extensive cell death response evident in early and advanced mammary tumors. Omics and drug-targeting studies revealed that PI3Ks act to reduce glucocorticoid receptor (GR) levels, which are rescued by loss of PTEN protein-phosphatase activity to restrain cell survival. The dual regulation of GR by PI3K and PTEN functions as a rheostat that can be exploited for the treatment of PTEN-loss driven cancers.
2020-10-15 | PXD016184 | Pride
Project description:miRNA pattern in hypoxic microenvironment of kidney cancer – role of PTEN
| PRJNA809699 | ENA
Project description:PTEN is implicated in a wide variety of pathophysiological conditions and traditionally studied in the context of the PIK3-AKT-mTOR axis. Recent studies from our group and others have reported a novel role of PTEN in the regulation of transcription at the genome-wide scale. This emerging role of PTEN on global transcriptional regulation is providing a better understanding of various diseases, including cancer. Since cancer progression is an energy-demanding process and PTEN is known to regulate metabolic processes, we sought to understand the role of PTEN in transcriptional regulation under metabolic stress, a condition often developing in the tumor microenvironment. In the present study, we demonstrate that PTEN modulates genome-wide RNA Polymerase II (Pol II) occupancy in cells undergoing glucose deprivation. The glucose-deprived PTEN null cells were found to continue global gene transcription, which may activate a survival mode. However, cells with constitutive PTEN expression slow transcription, an evolutionary mechanism that may save cellular energy and activate programmed cell death pathways, in the absence of glucose. Interestingly, alternative exon usage by PTEN null cells is increased under metabolic stress compared to PTEN expressing cells. Overall, our study comprehensively demonstrates distinct mechanisms involved in PTEN-dependent genome-wide transcriptional control under metabolic stress. Our findings provide a new insight in understanding the tumor microenvironment and how PTEN loss of function, whether by genetic or non-genetic mechanisms, can contribute to a favorable transcriptional program employed by tumor cells to escape apoptosis, hence developing more aggressive and metastatic phenotypes.
2020-09-04 | GSE152559 | GEO