Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

ABSTRACT: Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

ORGANISM(S): Homo Sapiens

SUBMITTER: Qi Wang

PROVIDER: PXD043632 | iProX | Mon Jul 10 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis.

Duan Wenzhe W Liu Wenwen W Xia Shengkai S Zhou Yang Y Tang Mengyi M Xu Mingxin M Lin Manqing M Li Xinyu X Wang Qi Q

Journal of translational medicine 20230816 1

<h4>Background</h4>Resistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown.<h4>Methods</h4>PEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells wi ...[more]

PMID: 37587486

Similar Datasets

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

Project description:Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

| PRJNA869568 | ENA

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

Project description:To investigate the function of AKR1B10 in the lung cancer brain metastasis cells, we established PC9-BrM3 cells in which AKR1B10 has been knocked down by shRNA.

2023-08-23 | GSE211215 | GEO

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis.

Project description:BackgroundResistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown.MethodsPEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interference in vitro and in vivo. Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches.ResultsThe lung cancer brain metastatic subpopulation cells (PC9-BrM3) exhibited significant resistance to PEM and silencing AKR1B10 in PC9-BrM3 increased the PEM sensitivity in vitro and in vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle.ConclusionsOur finding demonstrates that AKR1B10/glycolysis/H4K12la/CCNB1 promotes acquired PEM chemoresistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.

| S-EPMC10428599 | biostudies-literature

Brain metastasis from lung adenocarcinoma patients

Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. 28 brain metastasis samples: 19 from Marc Ladanyi 9 from William L. Gerald

2010-06-17 | E-GEOD-14108 | biostudies-arrayexpress

Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.

Project description:In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed. A remarkable synergistic effect between EGFR-TKI gefitinib and Bcl-2 inhibitors ABT-263 (0.17 ± 0.010 µM at 48 h and 0.02 ± 0.004 µM at 72 h), or ABT-199 (0.22 ± 0.008 µM at 48 h and 0.02 ± 0.001 µM at 72 h) to overcome acquired resistance to gefitinib (> 0.5 µM at 48 h and 0.10 ± 0.007 µM at 72 h) in PC-9-Br was observed in MTT assays. AZD9291 was also shown to overcome acquired resistance to gefitinib in PC-9-Br in MTT assays (0.23 ± 0.031 µM at 48 h and 0.03 ± 0.008 µM at 72 h). Western blot showed significantly decreased phospho-Erk1/2 and increased cleaved-caspase-3 expressions were potential synergistic mechanisms for gefitinib + ABT263/ABT199 in PC-9-Br. Significantly decreased protein expressions of phospho-EGFR, phospho-Akt, p21, and survivin were specific synergistic mechanism for gefitinib + ABT199 in PC-9-Br. In vivo studies demonstrated afatinib (30 mg/kg) and AZD9291 (25 mg/kg) could significantly reduce the LCBM in vivo and increase survival percentages of treated mice compared with mice treated with vehicle and gefitinib (6.25 mg/kg). In conclusion, our study demonstrated gefitinib + ABT263/ABT199, afatinib, and AZD9291 have clinical potential to treat LCBM.

| S-EPMC9511176 | biostudies-literature

Adaptive anoikis resistance promotes ovarian cancer metastasis

Project description:Adaptive anoikis resistance promotes ovarian cancer metastasis

| PRJNA1008671 | ENA

Proteomic reveals reasons for acquired drug resistance in lung cancer derived brain metastasis based on a newly established multi-organ microfluidic chip model

Project description:Anti-tumor drugs can effectively shrink the lesions of primary lung cancer; however, it has limited therapeutic effect on patients with brain metastasis (BM). A BM preclinical model based on a multi-organ microfluidic chip has been established proficiently in our previous work. In this study, the BM subpopulation (PC9-Br) derived from the parental PC9 cell line was isolated from the chip model and found to develop obvious resistance to antineoplastic drugs including chemotherapeutic agents (cisplatin, carboplatin, pemetrexed) and tyrosine kinase inhibitors (TKIs) which target epidermal growth factor receptor (EGFR); this suggested that the acquisition of drug-resistance by brain metastatic cells was attributable to the intrinsic changes in PC9-Br. Hence, we performed proteomic and revealed a greatly altered spectrum of BM protein expression compared with primary lung cancer cells.

2021-09-09 | PXD021760 | Pride

Brain metastasis from lung adenocarcinoma patients

Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.

2010-06-17 | GSE14108 | GEO

Acquired immunotherapy resistance in PDA

Project description:Acquired immunotherapy resistance in PDA

| PRJNA918626 | ENA

Transcriptomic profiling of Lung adenocarcinoma brain metastasis

Project description:Brain metastasis developed in nearly 40% of lung adenocarcinoma (LUAD) patients diagnosed with distant metastasis. There is lack of transcriptomic data of brain lesions from human lung adenocarcinoma patients. As part of the project to understanding the tumor microenvironment in brain metastasis of LUAD patients, we performed bulk RNA analysis on brain metastases from 6 LUAD patients. In order to understand the tumor intrinsic factors that potential shape the tumor microenvironment, we compared these data with bulk RNA sequencing data from 14 early stage and 11 late stage primary LUAD tumor from TCGA database. Pathway expression analysis showed a downregulation of pro-inflammatory signals in brain metastasis and upregulation of DNA synthesis and oxidative phosphorylation pathways related to rapid proliferation in brain lesions.

2019-12-10 | GSE141685 | GEO

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