Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [HOXC10]

ABSTRACT: A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [HOXC10]

PROVIDER: PRJNA487268 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers

Project description:A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers

| PRJNA487264 | ENA

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [inhibitors]

Project description:A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [inhibitors]

| PRJNA487269 | ENA

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [HOXC10]

Project description:HOXC10 overexpression modifies the therapeutic response to combined MEK and BRD4 inhibitors We performed microarray analysis of cells expressing LACZ or HOXC10 treated with MEK and BRD4 inhibition in combination for 24 hours, prior to the induction of cell death, to analyze transcriptional changes that might be mechanistic drivers of the therapeutic effect.

2020-04-02 | GSE118908 | GEO

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [inhibitors]

Project description:MEK and BRD4 inhibitors induce cell death of subset of KRAS-mutant lung tumors in vitro and in vivo We performed microarray analysis of MEK and BRD4 inhibition alone and in combination 24 hours after treatment, prior to the induction of cell death, to analyze transcriptional changes that might be mechanistic drivers of the therapeutic effect

2020-04-02 | GSE118903 | GEO

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers

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

2020-04-02 | GSE118909 | GEO

Oncogenic KRAS induces arginine auxotrophy in non-small cell lung cancer and confers a therapeutic vulnerability to SLC7A1 inhibition

Project description:The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer, yet our understanding about the regulatory mechanisms for this pathway in different types of cancer is very limited. In this study, we discover that oncogenic activation of KRAS in non-small cell lung cancer (NSCLC) silences the expression of arginosuccinate synthase 1 (ASS1), a urea cycle enzyme catalyzing the production of arginine from aspartate and citrulline, and thereby diverts the utilization of aspartate to pyrimidine synthesis to meet the high demand for DNA replication in KRAS-mutant NSCLC. Specifically, KRAS signaling facilitates a hypo-acetylated state in the promoter region of ASS1 gene in a histone deacetylase 3 (HDAC3)-dependent manner, which in turn impedes the recruitment of the transcription factor c-MYC for ASS1 transcription. ASS1 suppression in KRAS-mutant NSCLC cancer cells impairs the biosynthesis of arginine and renders growth dependency on SLC7A1, an arginine transmembrane transport, to import extracellular arginine. Depletion of SLC7A1 in both patient-derived organoid and xenograft models obtains a substantial therapeutic benefit in inhibiting KRAS-driven NSCLC growth. Together, our findings uncover a new role of oncogenic KRAS in rewiring urea cycle metabolism and identify SLC7A1-mediated arginine uptake as a therapeutic vulnerability in treating KRAS-mutant NSCLC.

2024-01-20 | GSE253688 | GEO

Regulatory integration of Hox factor action with Tbox factors in limb development

Project description:Hindlimb and Forelimb-specific Tbox factors integrates their mode of action with distinct Hox factors resulting in different transcriptional outcomes. In addition, hindlimb-specific Tbx4, Hoxc10 and Pitx1 act on the same platform to target common putative downstream genes for hindlimb development

2018-03-08 | GSE104398 | GEO

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [RNA-seq]

Project description:While Hox genes encode for similar transcription factors (TFs), they induce different fates across body axes. We sought to understand how Hox TF genomic binding preferences relate to their patterning activities during neuronal differentiation. To generate the required neuronal diversity for locomotor activity, Hox TFs specify spinal motor neuron and interneuron subtypes along the rostro-caudal axis. Our data revelated that Hoxc6 and Hoxc8 of the central group induce limb-innervating fates by binding to the same sites. On the other hand, the posterior group Hox genes assign different positional identities: Hoxc9 (thoracic), Hoxc10 (limb-innervating) and Hox13 (axial elongation termination) by binding to distinct sites with the same primary motif. We find that their genomic binding distributions are explained by differential abilities to bind to previously inaccessible chromatin. Thus, the vertebrate posterior Hox expansion and its associated patterning diversification is the product of their differential abilities to associate with less accessible chromatin.

2020-09-06 | GSE142378 | GEO

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ChIP-seq]

2020-09-06 | GSE142377 | GEO

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ATAC-seq]

2020-09-06 | GSE142375 | GEO