Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple negative breast cancer.

ABSTRACT: Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple negative breast cancer.

PROVIDER: PRJNA1090021 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR28397608_1.fastq.gz	Fastqsanger.gz
	SRR28397608_2.fastq.gz	Fastqsanger.gz
	SRR28397609_1.fastq.gz	Fastqsanger.gz
	SRR28397609_2.fastq.gz	Fastqsanger.gz
	SRR28397610_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 100

Similar Datasets

Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in TNBC

Project description:Cancer cell plasticity contributes significantly to failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a genome-wide CRISPR-Cas9 screen, we investigated escape-mechanisms of NOTCH-driven TNBC treated with a gamma-secretase inhibitor (GSI) and identified SOX2 as a target of resistance to Notch inhibition. We described a novel reciprocal inhibitory feedback mechanism between Notch signaling and SOX2. Specifically, Notch signaling inhibits SOX2 expression through its target genes of the HEY family, and SOX2 inhibits Notch signaling through direct interaction with RBPJ. This mechanism shapes divergent cell states with NOTCH positive TNBC being more epithelial-like, while SOX2 expression correlates with epithelial-mesenchymal transition, induces cancer stem cell features and GSI resistance. To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH-inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.

| S-SCDT-10_1038-S44321-024-00161-8 | biostudies-other

Chromatine immunoprecipitation (ChIP-seq) for RBPJ and SOX2 in Triple negative breast cancer MB157 cells and GSI-resistant MB157R cells upon induction of Notch1 or Sox2 signaling.

Project description:Cell plasticity of Triple negative breast cancer (TNBC) contributes to tumor heterogeneity and is one of the major reasons for the limited success of chemo- or combination therapies in the clinics. The molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance to chemo or targeted therapies are largely unknown. Using a genome wide CRISPR-Cas9 screen we investigated the escape mechanisms of Notch driven TNBC, when treated with targeted therapy. We describe molecularly a reciprocal inhibitory feedback mechanism between Notch signaling and the pluripotency associated transcription factor SOX2, which shapes divergent cell states, EMT, cancer stem cell features and associates with therapeutic response and escape to targeted therapy. Moreover, we performed and assessed monotherapy and drug combination treatments in Notch-inhibitor sensitive and resistant TNBC xenotransplant and identified combination and second line treatment options which were able to induce tumor control and reduce metastatic burden.

2024-10-25 | GSE262007 | GEO

Gene expression profiling of Triple Negative Breast Cancer MB157 cells and GSI-resistant MB157R cells upon induction of Notch1 or Sox2 signaling.

2024-10-25 | GSE262001 | GEO

Genome-wide loss-of-function CRISPR/Cas9 screen of Triple Negative Breast Cancer GSI-resistant MB157R cells treated with GSI or vehicle.

2024-10-25 | GSE270368 | GEO

Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple negative breast cancer.

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

2024-10-25 | GSE262009 | GEO

Identification the Expression of Sox2 in Colorectal Cancer Tissues

Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.

| 2124687 | ecrin-mdr-crc

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2

Project description:Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2

| PRJNA1120892 | ENA

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [Spatial Transcriptomics]

Project description:During development, the meninges act as a regulator of neocortical development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meninges-derived retinoic acid (RA) promotes neocortical progenitor cell cycle exit however the underlying mechanism is unknown. Here, we use Foxc1-mutant embryos that lack meninges-derived ligands, spatial transcriptomics, and profiling of retinoic-acid receptor-a (RARa) DNA binding to identify the neurogenic transcriptional mechanisms of RA signaling in cortical neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in the Sox2ot promoter, a long non-coding RNA that regulates Sox2 expression, and RA promotes Sox2ot expression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of howmeningeal RA coordinates neocortical development and insight into how defects in meningeal develop can cause neurodevelopmental disorders.

2024-09-25 | GSE269283 | GEO

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [CUT&Run]

2024-09-25 | GSE269282 | GEO

Notch

Project description:Notch

| PRJNA988118 | ENA