Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The NFIB/CARM1 Partnership is a Therapeutic Target for Small Cell Lung Cancer

ABSTRACT: This project identified NFI family members as CARM1 substrates. NFIB was previously reported to play a critical role in the development of small cell lung cancer. We provided evidence that the arginine methylation of NFIB is required for its oncogenic function in small cell lung cancer.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Bill Russell

PROVIDER: MSV000090746 | MassIVE | Sat Nov 19 07:31:00 GMT 2022

SECONDARY ACCESSION(S): PXD038217

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer.

Gao Guozhen G Hausmann Simone S Flores Natasha M NM Benitez Ana Morales AM Shen Jianjun J Yang Xiaojie X Person Maria D MD Gayatri Sitaram S Cheng Donghang D Lu Yue Y Liu Bin B Mazur Pawel K PK Bedford Mark T MT

Nature communications 20230123 1

The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator. Biochemical studies reveal that tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpre ...[more]

PMID: 36690626

Similar Datasets

The NFIB/CARM1 Partnership is a Therapeutic Target for Small Cell Lung Cancer

Project description:This project identified NFI family members as CARM1 substrates. NFIB was previously reported to play a critical role in the development of small cell lung cancer. We provided evidence that the arginine methylation of NFIB is required for its oncogenic function in small cell lung cancer.

2023-02-07 | PXD038237 | Pride

The NFIB/CARM1 Axis is a Therapeutic Target for Small Cell Lung Cancer

Project description:We identified NFIB as a CARM1 substrate and showed that this transcription factor utilizes CARM1 as a coactivator. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpressed in small cell lung cancer (SCLC). Using a SCLC mouse model, we show that both CARM1 and the CARM1 methylation site on NFIB are critical for the rapid onset of SCLC. By performing the high-throughput sequecing analysis, we found that CARM1-null and NFIB-R388K mutant mouse SCLC tumors share the ability to regulate chromatin accessbility and have similar gene expression pattern.

2022-02-07 | GSE195843 | 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

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

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

| PRJNA1066766 | ENA

Methylation of KRAS by SETD7 promotes KRAS degradation in non-small cell lung cancer

Project description:Oncogenic KRAS mutations are a key driver for initiation and progression in non-small-cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity remain largely unclear. Here, we show that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysines 182 and 184. SETD7-mediated methylation of KRAS leads to degradation of KRAS and attenuation of the RAS/MEK/ERK signaling cascade, endowing SETD7 with a potent tumor-suppressive role in NSCLC, both in vitro and in vivo. Mechanistically, RABGEF1, a ubiquitin E3 ligase of KRAS, was recruited and promoted KRAS degradation in a K182/K184 methylation-dependent manner. Notably, SETD7 is inversely correlated with KRAS at the protein level in clinical NSCLC tissues. Low SETD7 or RABGEF1 expression is associated with poor prognosis in lung adenocarcinoma patients. Altogether, our results elucidate a tumor-suppressive function of SETD7 that operates via modulating KRAS methylation and degradation.

2023-07-19 | PXD043931 |

Small Cell Lung Cancer

Project description:Small Cell Lung Cancer

| PRJNA314262 | ENA

Small cell lung cancer

Project description:Small cell lung cancer

| PRJNA672692 | ENA

MAX-mutant small cell lung cancers exhibit impaired activities of MGA-dependent ncPRC1.6.

Project description:The MYC axis is commonly disrupted in cancer, mostly by activation of the MYC family of oncogenes, but also by genetic inactivation of MAX, the obligate partner of MYC, and of the MAX partner, MGA, both of which are members of the polycomb repressive complex, ncPRC1.6. While the oncogenic properties of the MYC family have been extensively studied, the tumor suppressor functions of MAX and MGA and the role of the MYC genes in MAX-mutant cells remain unclear. To address these knowledge gaps, we used chromatin immunoprecipitation, RNA-sequencing and mass spectrometry-based proteomic analysis in MAX-restituted and MYC oncogenic-transformed cell lines derived from human small cell lung cancer (SCLC), which is a high-grade neuroendocrine type of lung cancer. We found that MAX-mutant SCLC cells express ASCL1 and ASCL1-dependent targets, implying that these cells belong to the ASCL1-dependent group of SCLCs. In the absence of MAX, even after ectopic overexpression of MYC, we found no recruitment of MYC to the DNA. Furthermore, MAX reconstitution triggered pro-differentiation expression profiles that shifted when MAX and oncogenic MYC were co-expressed. Although ncPRC1.6 could be formed, the lack of MAX restricted global MGA occupancy, selectively driving its recruitment towards E2F6 motifs. Conversely, MAX restitution enhanced MGA occupancy and global gene repression of genes involved in different functions, including stem-cell and DNA repair/replication. Our data reveal that MAX-mutant SCLCs have ASCL1 characteristics, and are MYC-independent, and that their oncogenic features include deficient ncPRC1.6-mediated gene repression.

2021-09-22 | PXD017658 | Pride

The NFIB/CARM1 Axis is a Therapeutic Target for Small Cell Lung Cancer

Project description:The NFIB/CARM1 Axis is a Therapeutic Target for Small Cell Lung Cancer

| PRJNA802265 | ENA

Non-small-cell lung tumor and normal lung tissue methylation

Project description:Using paired tumor and non-tumor lung tissues from 47 individuals we identified common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation status using Illumina GoldenGate arrays. For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGM-bM-^@M-^Ys with the greatest change in methylation associated with tumor development. Using paired tumor and non-tumor lung tissues from 47 individuals we identified common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation status using Illumina GoldenGate arrays. For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGM-bM-^@M-^Ys with the greatest change in methylation associated with tumor development.

2012-07-02 | E-GEOD-27902 | 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