Immunological Data Discovery Index
Immunological Data Discovery Index
| identifier: | SDY1079 |
| description: |
The molecular mechanism of lung cancer metastatic remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival. Small-scale in vivo screening identified several genes, including Cd109, that encode novel pro-metastatic factors. We uncovered signaling mediated by Janus kinases (Jaks) and the transcription factor Stat3 as a critical, pharmacologically targetable effector of CD109-driven lung cancer metastasis. In summary, by coupling the systematic genomic analysis of purified cancer cells in distinct malignant states from mouse models with extensive human validation, we uncovered several key regulators of metastatic ability, including an actionable pro-metastatic CD109?Jak?Stat3 axis
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| aggregation: |
instance of dataset
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| refinement: |
2 - Complete set of descriptive data and results, as ascertained by ImmPort.
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| availability: |
available with registration
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| primaryPublications: |
28191885 |
| isAbout: |
The study objectives are to leverage tumor barcoding in a mouse model of human lung adenocarcinoma to identify neoplastic cells at defined stages of metastatic progression, Use unbiased genomic analysis and a small-scale in vivo functional screen to uncover novel drivers of metastatic ability, to couple these analyses with extensive human validation, functional metastasis assays in vivo, and molecular analyses, to identify a targetable pro-metastatic CD109?Jak?Stat3 axis.
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| authorizations: |
registration required
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| accessURL: |
https://www.ncbi.nlm.nih.gov/bioproject/PRJNA329195 https://aspera-immport.niaid.nih.gov:9443/browser?path=SDY1079 |
| landingPage: |
http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY1079 |
| clinical trial: | |
| study category: | No Research Focus Specified |
| study type: | Intervention Longitudinal |
| subject species: | Mus musculus |
| biosample type: |
Lung Other |
| subject gender: | Unknown |
| assay type: | RNA sequencing |
| name: |
metatastic lung cancer
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| fullName: |
Monte Winslow
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| affiliations: |
Stanford University School of Medicine
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| roles: |
principal investigator
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| name: |
A targetable CD109-Janus kinase-Stat axis in metastatic lung cancer.
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| size: |
2
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| output: |
The study endpoints include Mouse ex vivo RNAseq data and result, RNAseq data and result on Cd109 knockdown cells, Cell culture assays (low-density plating assay, anchorage-independent growth assays, Cell line transplantation and analysis, Small-scale in vivo screening on drivers of matastatic ability ( Cd109 is identified), Generation of Cd109-knockout lines, Functional analysis on Cd109 effectors ( Western blotting and sh knockdown), and Jak kinase inhibitor (pyridone 6) treatments results (immunohistochemistry)
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| studyGroups: |
KPT-Met2distant: Distant metastasis, including soft tissue and liver, tumor genotype KPT: KrasLSL-G12D/+
p53flox/flox
R26LSL-tdTomato
KT- Hyperplasia: Hyperplasia, tumor genotype KT: KrasLSL-G12D/+
KPT-Met2Lymph Node: Lymph Node metastasis, tumor genotype KPT: KrasLSL-G12D/+
KPT-Tmet: Metastatic primary tumor, tumor genotype KPT: KrasLSL-G12D/+
KPT-TnonMet: Non-metastatic primary tumor, tumor genotype KPT: KrasLSL-G12D/+
KPT-Normal lung: Normal lung, tumor genotype KPT: KrasLSL-G12D/+
KPT-Early: p53 deficient hyperplasia, collected at 10 wks after tumor initiation, tumor genotype KPT: KrasLSL-G12D/+
KPT-DTC: Pleural Cavity Disseminating tumor cells, tumor genotype KPT: KrasLSL-G12D/+
KPT-Pleural-met: Pleural metastasis, tumor genotype KPT: KrasLSL-G12D/+
R26LSL-tdTomato.
889PF-shGFP: 889PF-shGFP
889PF-shCd109: 889PF-shCd109
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| description: |
By coupling the systematic genomic analysis of purified cancer cells in distinct malignant states from mouse models with extensive human validation, we uncovered several key regulators of metastatic ability, including an actionable pro-metastatic CD109?Jak?Stat3 axis.
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| identifier: |
10.21430/M3HC3F4A8X
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| startDate: |
2014-11-08
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| name: |
ImmPort
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| identifier: |
SCR:012804
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| homePage: |
http://www.immport.org |
