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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/20072
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dc.contributor.authorSingh S.-
dc.contributor.authorKumar, Sushil-
dc.contributor.authorSrivastava R.K.-
dc.contributor.authorNandi A.-
dc.contributor.authorThacker G.-
dc.contributor.authorMurali H.-
dc.contributor.authorKim S.-
dc.contributor.authorBaldeon M.-
dc.contributor.authorTobias J.-
dc.contributor.authorBlanco M.A.-
dc.contributor.authorSaffie R.-
dc.contributor.authorZaidi M.R.-
dc.contributor.authorSinha S.-
dc.contributor.authorBusino L.-
dc.contributor.authorFuchs S.Y.-
dc.contributor.authorChakrabarti R.-
dc.date.accessioned2022-02-17T11:27:31Z-
dc.date.available2022-02-17T11:27:31Z-
dc.date.issued2020-
dc.identifier.citationNature Cell Biology, 22(5): 591-602-
dc.identifier.issn14657392-
dc.identifier.other32284542-
dc.identifier.urihttps://doi.org/10.1038/s41556-020-0495-y-
dc.identifier.urihttp://repository.iitr.ac.in/handle/123456789/20072-
dc.description.abstractTriple-negative breast cancer (TNBC) is characterized by a high degree of immune infiltrate in the tumour microenvironment, which may influence the fate of TNBC cells. We reveal that loss of the tumour suppressive transcription factor Elf5 in TNBC cells activates intrinsic interferon-γ (IFN-γ) signalling, promoting tumour progression and metastasis. Mechanistically, we find that loss of the Elf5-regulated ubiquitin ligase FBXW7 ensures stabilization of its putative protein substrate IFN-γ receptor 1 (IFNGR1) at the protein level in TNBC. Elf5low tumours show enhanced IFN-γ signalling accompanied by an increase of immunosuppressive neutrophils within the tumour microenvironment and increased programmed death ligand 1 expression. Inactivation of either programmed death ligand 1 or IFNGR1 elicited a robust anti-tumour and/or anti-metastatic effect. A positive correlation between ELF5 and FBXW7 expression and a negative correlation between ELF5, FBXW7 and IFNGR1 expression in the tumours of patients with TNBC strongly suggest that this signalling axis could be exploited for patient stratification and immunotherapeutic treatment strategies for Elf5low patients with TNBC. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.-
dc.language.isoen_US-
dc.publisherNature Research-
dc.relation.ispartofNature Cell Biology-
dc.subjectF box/WD repeat containing protein 7-
dc.subjectgamma interferon-
dc.subjectgamma interferon receptor 1-
dc.subjectprogrammed death 1 ligand 1-
dc.subjectSTAT3 protein-
dc.subjecttranscription factor-
dc.subjecttranscription factor Elf5-
dc.subjectubiquitin protein ligase-
dc.subjectunclassified drug-
dc.subjectDNA binding protein-
dc.subjectELF5 protein, human-
dc.subjectF box/WD repeat containing protein 7-
dc.subjectFBXW7 protein, human-
dc.subjectgamma interferon-
dc.subjectgamma interferon receptor-
dc.subjectinterferon receptor-
dc.subjecttranscription factor-
dc.subjectanimal cell-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectanimal tissue-
dc.subjectArticle-
dc.subjectcancer prognosis-
dc.subjectcell loss-
dc.subjectcontrolled study-
dc.subjectdistant metastasis free survival-
dc.subjectdrug efficacy-
dc.subjectepithelium cell-
dc.subjectfemale-
dc.subjecthuman-
dc.subjectimmunohistochemistry-
dc.subjectimmunosuppressive treatment-
dc.subjectlung metastasis-
dc.subjectmetastasis-
dc.subjectmetastasis potential-
dc.subjectmouse-
dc.subjectneutrophil-
dc.subjectnonhuman-
dc.subjectoverall survival-
dc.subjectphenotype-
dc.subjectpriority journal-
dc.subjectprotein expression-
dc.subjectprotein function-
dc.subjectprotein stability-
dc.subjectRNA sequencing-
dc.subjectsignal transduction-
dc.subjectsurvival rate-
dc.subjectsurvival time-
dc.subjecttriple negative breast cancer-
dc.subjecttumor growth-
dc.subjecttumor microenvironment-
dc.subjecttumor volume-
dc.subjecttumor xenograft-
dc.subjectanimal-
dc.subjectBagg albino mouse-
dc.subjectcell line-
dc.subjectcell proliferation-
dc.subjectHEK293 cell line-
dc.subjectmetabolism-
dc.subjectmetastasis-
dc.subjectpathology-
dc.subjectphysiology-
dc.subjectsignal transduction-
dc.subjecttriple negative breast cancer-
dc.subjecttumor cell line-
dc.subjectAnimals-
dc.subjectCell Line-
dc.subjectCell Line, Tumor-
dc.subjectCell Proliferation-
dc.subjectDNA-Binding Proteins-
dc.subjectF-Box-WD Repeat-Containing Protein 7-
dc.subjectFemale-
dc.subjectHEK293 Cells-
dc.subjectHumans-
dc.subjectInterferon-gamma-
dc.subjectMice-
dc.subjectMice, Inbred BALB C-
dc.subjectNeoplasm Metastasis-
dc.subjectReceptors, Interferon-
dc.subjectSignal Transduction-
dc.subjectTranscription Factors-
dc.subjectTriple Negative Breast Neoplasms-
dc.subjectTumor Microenvironment-
dc.titleLoss of ELF5–FBXW7 stabilizes IFNGR1 to promote the growth and metastasis of triple-negative breast cancer through interferon-γ signalling-
dc.typeArticle-
dc.scopusid57189686345-
dc.scopusid57213855617-
dc.scopusid6603663872-
dc.scopusid57216244266-
dc.scopusid57021593500-
dc.scopusid57216364425-
dc.scopusid57204683725-
dc.scopusid57216372871-
dc.scopusid7202182919-
dc.scopusid56733790800-
dc.scopusid57200689664-
dc.scopusid57193396546-
dc.scopusid7403739042-
dc.scopusid6602435324-
dc.scopusid57203074493-
dc.scopusid16149432900-
dc.affiliationSingh, S., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationKumar, S., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationSrivastava, R.K., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationNandi, A., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationThacker, G., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationMurali, H., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationKim, S., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationBaldeon, M., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationTobias, J., Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationBlanco, M.A., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationSaffie, R., Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationZaidi, M.R., Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States-
dc.affiliationSinha, S., Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY, United States-
dc.affiliationBusino, L., Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationFuchs, S.Y., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.affiliationChakrabarti, R., Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States-
dc.description.fundingWe thank L. King (University of Pennsylvania) for critical reading of the manuscript and helpful discussions. We thank A. Minn (University of Pennsylvania) for helpful discussions. We thank the Penn Vet Comparative Pathology Core for assistance with embedding, sectioning and consultation on tumour sample analysis. We thank Y. Kang (Princeton University) for the HEK293T, EpRas, 4T1, LM2 and BT549 cell lines. We thank S. Ran (Southern Illinois University) for the HCC1806 cell line. We thank the Eastern Division of the Cooperative Human Tissue Network at The University of Pennsylvania for providing human breast cancer fixed tissues from patients. We thank A. Welm (University of Utah) for the PDX tumour tissues. We thank the members of the Flow Cytometry Core at the Children’s Hospital of Philadelphia and University of Pennsylvania. We thank the Penn Vet Imaging Core for confocal microscopy. This work was supported by grants from the American Cancer Society, an NCI-K22 grant to R.C. (K22CA193661-01) and an NCI-R01 (R01 CA237243-01A1) grant to R.C. American Cancer Society, ACS: K22CA193661-01, R01 CA237243-01A1; National Cancer Institute, NCI: K22CA193661, R01CA193711-
dc.description.correspondingauthorChakrabarti, R.; Department of Biomedical Sciences, United States; email: rumela@vet.upenn.edu-
Appears in Collections:Journal Publications [BT]

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