Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

1.Effects of L013 treatment on gene expression in KYSE150 and KYSE510 cells. 2. 5 Patient-derived organoids RNA-seq data

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) patients with the NRF2 oncogenic activation (NRFA) subtype have poor prognosis and limited response to conventional therapies due to excessive NRF2 accumulation. Here, through high-content screening of 725 CRBN ligand-based PROTACs, we identified L013 as an efficient NRF2 degrader. L013 reduces NRF2 in ESCC cells through dual mechanisms, including ubiquitination-mediated proteasomal degradation and suppression of NRF2 transcription. Functional studies showed that L013 inhibits the proliferation and tumorigenic capacity of NRF2-hyperactivated ESCC cells. In preclinical models, L013 lowered NRF2 levels and suppressed tumor growth in ESCC or lung squamous cell carcinoma (LUSC) patient-derived organoids and xenograft models, while showing acceptable safety. These findings identify L013 as a promising therapeutic candidate for NRFA-subtype ESCC and support a new strategy for targeting NRF2-driven oncogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324866 | GEO | 2026/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Differential squamous cell fates elicited by NRF2 gain-of-function versus KEAP1 loss-of-function

Project description:Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we challenged to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer-driver mutant Trp53R172H. Concomitant expression of NRF2L30F and Trp53R172H induced proliferation of squamous cell epithelia and resulted in NRF2-activated ESCC-like lesions. In contrast, while squamous cell-specific deletion of KEAP1 induced similar NRF2 hyper-activation, the loss-of-KEAP1 combined with Trp53R172H did not elicit the proliferation and formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappeared from the esophageal epithelium over time by cell competition. These findings provide insights into the observation that somatic mutations are more frequently observed in NRF2 than in KEAP1, and the mouse model developed here will be instrumental in elucidating the mechanistic basis leading to NRF2-activated ESCC.

2024-03-22 | GSE255927 | GEO

African American esophageal squamous cell carcinoma expression profile reveals loss of detox networks

Project description:Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is generally unresponsive to therapy. African Americans have an increased risk for esophageal squamous cell cancer (ESCC), the subtype that shows marked variation in geographic frequency. To identify key genes involved in ESC carcinogenesis in African Americans we conducted microarray expression profiling and found a significant dysregulation of genes encoding stress response and drug-metabolizing enzymes, mainly in NRF2 pathway. The involvement of NRF2 mediated oxidative damage represent a key step in the evolution of African American ESCC. Loss of activity of these enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence of ESCC in this ethnic group. The differential expression profile also indicates an inflammatory component and tissue regeneration in ESCC tumorigenesis. Together, these findings suggest a remarkable interplay of genetic and environmental factors in the pathogenesis of African American ESCC.

2017-08-15 | GSE77861 | GEO

Proteome of ESCC identified by LC-MS/MS

Project description:Protein identification in esophageal squamous cell carcinoma(ESCC) was performed,we explored the proteomic landscape in ESCC and attempted to perform clinical-related patient classification based on ESCC proteome.

2026-06-15 | PXD053809 | Pride

RNA-seq analysis in esophageal squamous cell carcinoma (ESCC) cell line KYSE510

Project description:RNA-seq analysis in esophageal squamous cell carcinoma (ESCC) cell line KYSE510

| PRJNA791214 | ENA

Differential protein expression between ESCC and normal tissues

Project description:To understand the difference of protein expression between paired esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues, we collected 10 paired ESCC and normal tissues from surgical resected specimems for high-throughput proteomic experiments. From comparative analysis, the dysregulated signaling pathways in ESCC could be uncovered.

2020-08-11 | PXD019834 | Pride

Gene expression analysis following depletion of LOXL2 in esophgeal cancer cells

Project description:Esophageal cancer is the sixth most common cause of cancer death globally, of which esophageal squamous cell carcinoma (ESCC) is the most common histological subtype. High level expression of LOXL2 has been shown to be associated with tumor metastasis and poor clinical outcome in ESCC. To determine whether there are genes whose expression in ESCC cells is regulated by LOXL2, next generation RNA sequencing analysis was used to compare the RNA expression profile of KYSE510 cells before and after silencing LOXL2 expression.

2020-08-01 | GSE135510 | GEO

Gene expression in normal and tumoral esophageal squamous cell lines

Project description:This study was designed to identify genes aberrantly expressed in esophageal squamous cell carcinoma (ESCC) cells. Three esophageal squamous cell carcinoma-derived cell lines and one normal human esophageal squamous cell line were analyzed.

2014-09-20 | E-GEOD-61587 | biostudies-arrayexpress

Microarray expression profile and functional analysis of circular RNAs in plasma for Esophageal Squamous Cell Carcinoma

Project description:The purpose of this study is to explore the circRNAs expression profiles in the plasma from esophageal squamous cell carcinoma (ESCC) patients.The purpose of this study is to explore the circRNAs expression profiles in the plasma from esophageal squamous cell carcinoma (ESCC) patients.

2021-03-23 | GSE112496 | GEO

Genome-wide methylation analysis of esophageal squamous cell carcinoma using Infinium HumanMethylation 450 BeadChip

Project description:DNA methylation in esophageal squamous cell carcinoma (ESCC)

2016-06-30 | GSE74693 | GEO

Squamous esophagus

Project description:SAGE libraries made of squamous esophagus tissue, primary cell culture or esophageal squamous cell carcinoma Keywords: SAGE analysis of different tissues squamous esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. primary cell culture was from 1 male Barrett's esophagus patient. Esophageal squamous cell carcinoma was from a patient known to have ESCC

2006-06-28 | E-GEOD-5154 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data