Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype

ABSTRACT: Crosstalk between tumor and stromal cells is essential for tumor pathogenesis. Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs), among others. Small EVs (≤200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrated that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to stromal cells. In this study, we performed RNA sequencing to explore the gene signature alterations in small EVs after knockdown GOF p53 expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148698 | GEO | 2020/11/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype [microarray]

Project description:We demonstrated that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblast cells. We used microarrays to determine the gene expression of NoF 151 fibroblasts after treating with small EVs from HT29-ntsh and -shP53 cells.

2021-01-06 | GSE164248 | GEO

Mutant p53 interactome study with IP-MS

Project description:Inactivating TP53 mutations lead to a loss of function of p53, but can also often result in oncogenic gain-of-function (GOF) of mutant p53 (mutp53) proteins which promote tumor development and progression. The GOF activities of TP53 mutations are well documented, but the mechanisms involved remain poorly understood. Here, we study the mutp53 interactome with IP-MS.

2023-11-27 | PXD047094 | Pride

Mutant p53 promotes tumor progression by the endoplasmic reticulum UDPase ENTPD5

Project description:Mutations in the p53 tumor suppressor gene are the most frequent genetic alteration in cancer and often associated with progression from benign to invasive, metastatic stages. Mutations inactivate tumor suppression by p53 and endow the protein with novel gain-of-function (GOF) activities that actively promote tumor progression, metastasis and therapy resistance. By comparative gene expression profiling of p53-mutated and p53-depleted cancer cells we identified ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) as a mutant p53 (mutp53) target gene. A comprehensive pan-cancer analysis revealed a highly significant correlation between GOF p53 mutations and elevated expression of ENTPD5. Mechanistically, regulation of ENTPD5 by mutp53 is mediated by the histone H3 lysine 4 (H3K4) methyltransferase COMPASS complex. ENTPD5 has been shown to function in the endoplasmic reticulum as a UDPase to promote the N-glycosylation and folding of membrane proteins such as growth factor receptors and integrins. We show ENTPD5 to be a mediator of mutp53 GOF activity in clonogenic growth, architectural tissue remodeling, migration, invasion, and lung colonization in an experimental metastasis mouse model. Our study reveals N-glycosylation in the endoplasmic reticulum as a novel mechanism underlying the progression of tumors with mutp53 that could provide new possibilities for treating cancers driven by GOF p53 mutations.

2016-11-29 | E-MTAB-4672 | biostudies-arrayexpress

exosomal ELNAT1 promotes lymphatic metastasis of bladder cancer

Project description:The crosstalk between tumor cells and LECs triggers the LN metastasis in bladder cancer (BCa), but the underlying mechanisms are not completely understood. Previously, we identified that BCa-secreted extracellular vesicles (EVs)-packaged lncRNAs mediated the communication with LECs and promoted LN metastasis. To evaluate whether EV-packaged lncRNAs triggered the LN metastasis of BCa, next-generation sequencing (NGS) to the global expression profiles of lncRNAs was utilized in the urinary EVs (urinary-EV) of five MIBC patients and five healthy volunteers.

2020-11-16 | GSE156308 | GEO

A cancer associated fibroblast hierarchy driven by mutant p53 induces perlecan deposition in the pancreatic tumor stroma to permit metastasis and impairs response to chemotherapy

Project description:Heterogeneous sub-populations of cancer cells exist within pancreatic tumors and shape the local stroma. Recent studies have provided evidence that subtypes of cancer-associated fibroblasts (CAFs) also coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 (loss or gain-of-function) manipulate CAFs using matched CAFs and cancer cells isolated from the low metastatic KPflC (p53 null) and highly metastatic KPC (gain-of-function p53 mutant) mouse models of pancreatic cancer. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that drive the establishment of a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. Using proteomic characterization of CAF secretomes combined with CRISPR-Cas9 based editing identified perlecan as a key component of this pro-metastatic and resistant environment. Lastly, using longitudinal intravital imaging with a CDK1 FRET reporter and titanium windows, we observe that these dominant CAFs delay cancer cell response to gemcitabine/Abraxane in both GOF and null p53 cancer cells. We also reveal that depletion of perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential novel target for development of anti-stromal therapies in pancreatic cancer.

2019-06-06 | GSE123646 | GEO

Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-cell acute lymphoblastic leukemia patients

Project description:Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative regulation of the cell cycle, suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. Overall, this signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.

2023-12-03 | GSE239467 | GEO

Mutant p53R273H regulated microRNA profiling in presence and absence of DNA damage in H1299 cells

Project description:In the present study, we used a high-throughput small RNA deep sequencing followed by a systematic computational analysis to identify genome wide mutant p53R273H regulated miRNAs in both DNA damage dependent and independent context. Several miRNA-mRNA regulatory networks have been predicted that might contribute to mutant p53 GOF properties. Differentially regulated miRNA signature profile has been validated in the lung cancer patients harboring wildtype and mutant p53. We identified specific miRNA signatures for lymph node metastasis associated with p53 mutation in lung adenocarcinoma and also predicted the possible contribution of two mutant p53 regulated miRNAs in EMT process. Furthermore, this study identified a hitherto unknown miRNA in human which might act as one of the crucial downstream targets of GOF mutant p53 to confer oncogenic properties. Determination of mutant p53R273H regulated microRNAs H1299 cells.

2017-04-28 | E-GEOD-68353 | biostudies-arrayexpress

Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants (RNA-Seq)

Project description:To identify mutant p53 GOF, murine primary osteosarcomas expressing p53R172H or p53R245W over null and p53-null osteosarcomas were processed for bulk sequencing; DEGs were identified in p53R172H and p53R245W expressing tumors by comparing to p53-null tumors; DEGs were used to identify dysregulated pathways and mutant p53 GOF

2023-05-12 | GSE231849 | GEO

Prevalent p53 gain-of-function mutants co-opt epigenetic pathways to drive cancer growth

Project description:We investigated the genomewide binding pattern of prevalent p53 gain-of-function (GOF) mutants by ChIP-seq, in a panel of breast cancer cell lines. We assessed the genomewide changes of H3K4me3 upon GOF p53 knockdown in MDA-MB-468 breast cancer cells bearing the p53 R273H mutation.

2015-07-31 | GSE59176 | GEO

Mutant p53R273H regulated microRNA profiling in presence and absence of DNA damage in H1299 cells

2017-04-28 | GSE68353 | GEO