Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE224567 | GEO | 2023/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas [RNA-Seq]

Project description:Lineage plasticity has been proposed as a major source of intratumoral heterogeneity and therapeutic resistance. Employing an inducible genetic engineered mouse model, we illustrate that lineage plasticity enables advanced Pancreatic Ductal Adenocarcinoma (PDAC) tumors to develop spontaneous relapse following elimination of the central oncogenic driver - Yap. Transcriptomic and immunohistochemistry analysis of a large panel of PDAC tumors reveals that within high-grade tumors, small niches of PDAC cells gradually evolve to re-activate pluripotent transcription factors (PTFs), which lessen their dependency on Yap. Comprehensive Cut&Tag analysis demonstrate that although acquisition of PTF expression is coupled with the process of epithelial-to-mesenchymal transition (EMT), PTFs form a core transcriptional regulatory circuitry (CRC) with Jun to overcome Yap dependency, which is distinct from the classic TGFb-induced EMT-TF network. A chemical-genetic screen and follow-up functional studies establish Brd4 as an epigenetic gatekeeper for the PTF-Jun CRC, and strong synergy between BET and Yap inhibitors in blocking PDAC growth.

2023-03-02 | GSE224566 | GEO

Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas [Cut&Tag]

2023-01-11 | GSE210412 | GEO

Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia.

Project description: Not available

| S-EPMC5464975 | biostudies-literature

A Yap-Myc-Sox2-p53 Regulatory Network Dictates Metabolic Homeostasis and Differentiation in Kras-Driven Pancreatic Ductal Adenocarcinomas.

Project description: Not available

| S-EPMC6783361 | biostudies-literature

Mature tertiary lymphoid structures are key niches of tumor-specific immune responses in pancreatic ductal adenocarcinomas

Project description:Objective: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalization into tertiary lymphoid structures (TLSs) for the generation of local antitumor immunity. Design: We characterized the functional states and spatial organization of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolor immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. Additionally, we performed a pan-cancer analysis of tumor-infiltrating T cells using scRNA-seq and single-cell T cell receptor sequencing (scTCR-seq) datasets from 8 cancer types. To evaluate the clinical relevance of our findings we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial. Results: We found that a subset of PDACs harbors fully developed TLSs where B cells proliferate and differentiate to plasma cells. These mature TLSs also support T cell activity and are enriched with tumor-reactive T cells. Importantly, we showed that chronically activated, tumor-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organizers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13+ tumor-infiltrating T cells across multiple cancer types further indicated a conserved link between tumor-antigen recognition and the allocation of B cells within sheltered hubs in the tumor microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pre-treatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens. Conclusion: We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

2023-06-01 | GSE226840 | GEO

Modeling oncogene addiction using RNA interference.

Project description: Not available

| S-EPMC2517605 | biostudies-literature

Mechanism of Oncogene Addiction

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-20 | GSE75058 | GEO

Mechanism of Oncogene Addiction

Project description:Mechanism of Oncogene Addiction

| PRJNA302297 | ENA

Targeting Non-Oncogene Addiction for Cancer Therapy.

Project description: Not available