Angiogenin/ribonuclease 5 is an EGFR ligand and a serum biomarker for erlotinib sensitivity in pancreatic cancer
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ABSTRACT:
PROVIDER: PRJNA432337 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin/ANG) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a previously unrecognized role of ANG as a serum biomarker, which may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.
2018-04-18 | GSE109427 | GEO
Project description: Not available
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Project description:Severe angiopathy is a major driver for diabetes associated secondary complications. Knowledge on underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5+ stromal precursors (SPs) at the edge of non-healing diabetic wounds in a murine db/db model, closely mirroring human type II diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5+ SPs. This compensates for the profoundly reduced angiogenin expression in non-treated murine and human chronic diabetic wounds. Silencing of angiogenin in ABCB5+ SPs prior to injection significantly reduced angiogenesis, reduced numbers of M2 macrophages and delayed wound closure in diabetic db/db mice implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining SPs-based therapies of non-healing diabetic foot ulcers and other pathologies with impaired angiogenesis.
2021-08-12 | GSE181881 | GEO
Project description:Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment. We used microarrays to detail global gene expression changes in EGFR mutant cells vs. WT cells responding to erlotinib. 4 EGFR mutant and 4 WT NSCLC cells were treated with or without erlotinib for 24 hr, followed by RNA extraction and hybridization on Affymetrix microarrays.
2014-05-16 | E-GEOD-57156 | biostudies-arrayexpress
Project description:Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment. We used microarrays to detail global gene expression changes in EGFR mutant cells vs. WT cells responding to erlotinib.
2014-05-16 | GSE57156 | GEO
Project description:Human Angiogenin (hAng) is a member of the ribonuclease A superfamily and a potent inducer of neovascularization. Herein, protein interactions of hAng in the nucleus and cytoplasm of the human umbilical vein cell line EA.hy926, have been investigated by mass spectroscopy. The first gel-free analysis of hAng immunoprecipitates from the cytoplasmic and nuclear extracts from EA.hy926 cancer human cell line, revealed many statistically significant potential hAng-interacting proteins. The majority of the proteins identified by the mass spectrometry analysis are parts of multiprotein complexes, and some of them are common in nucleus and cytoplasm, including spliceosome, proteasome, and molecular chaperone TRiC/CCT. These complexes are involved in crucial biological pathways, implicating thus the key role of hAng in many vital cellular processes.
2017-08-11 | PXD006584 | Pride
Project description:Human Angiogenin (hAng) is a member of the ribonuclease A superfamily and a potent inducer of neovascularization. Herein, protein interactions of hAng in the nucleus and cytoplasm of the human umbilical vein cell line EA.hy926, have been investigated by mass spectroscopy. The first gel-free analysis of hAng immunoprecipitates from the cytoplasmic and nuclear extracts from EA.hy926 cancer human cell line, revealed many statistically significant potential hAng-interacting proteins. The majority of the proteins identified by the mass spectrometry analysis are parts of multiprotein complexes, and some of them are common in nucleus and cytoplasm, including spliceosome, proteasome, and molecular chaperone TRiC/CCT. These complexes are involved in crucial biological pathways, implicating thus the key role of hAng in many vital cellular processes.
2017-08-11 | PXD006583 | Pride
Project description:Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.
2020-01-24 | GSE144169 | GEO
Project description:This experiment is designed to detect genes differentially expressed in 2uM erlotinib treatment versus DMSO treatment and to identify differential gene set enrichments.
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Project description:We were interested in characterizing the transcriptional changes that occur on a genome-wide scale following treatment of EGFR-mutant lung cancer cells with targeted therapies. HCC827 human lung cancer cells harboring an amplified EGFR allele with an activating in frame deletion of 15 nucleotides in exon 19 were treated in triplicate with 1uM erlotinib (EGFR inhibitor), AZD-6244 (MEK inhibitor) or BEZ-235 (PI3-Kinase/mTOR inhibitor) for 6 hours, followed by total mRNA isolation and whole transcriptome analysis using Affymetrix U133 Plus 2.0 expression arrays.
2015-02-25 | E-GEOD-51212 | biostudies-arrayexpress