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dc.contributor.authorHARIKRISHNAN, KEERTHIen_US
dc.contributor.authorJOSHI, OMKARen_US
dc.contributor.authorMADANGIRIKAR, SAILIen_US
dc.contributor.authorBALASUBRAMANIAN, NAGARAJen_US
dc.date.accessioned2020-08-14T07:16:04Z-
dc.date.available2020-08-14T07:16:04Z-
dc.date.issued2020-07en_US
dc.identifier.citationFrontiers in Cell and Developmental Biology, 8.en_US
dc.identifier.issn2296-634Xen_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/4952-
dc.identifier.urihttps://doi.org/10.3389/fcell.2020.00522en_US
dc.description.abstractEpidermal Growth Factor Receptor (EGFR) is a known promoter of tumor progression and is overexpressed in lung cancers. Growth factor receptors (including EGFR) are known to interact with extracellular matrix (ECM) proteins, which regulate their activation and function. Fibulin-1 (FBLN1) is a major component of the ECM in lung tissue, and its levels are known to be downregulated in non-small cell lung cancers (NSCLC). To test the possible role FBLN1 isoforms could have in regulating EGFR signaling and function in lung cancer, we performed siRNA mediated knockdown of FBLN1C and FBLN1D in NSCLC Calu-1 cells. Their loss significantly increased basal (with serum) and EGF (Epidermal Growth Factor) mediated EGFR activation without affecting net EGFR levels. Overexpression of FBLN1C and FBLN1D also inhibits EGFR activation confirming their regulatory crosstalk. Loss of FBLN1C and FBLN1D promotes EGFR-dependent cell migration, inhibited upon Erlotinib treatment. Mechanistically, both FBLN1 isoforms interact with EGFR, their association not dependent on its activation. Notably, cell-derived matrix (CDM) enriched FBLN1 binds EGFR. Calu-1 cells plated on CDM derived from FBLN1C and FBLN1D knockdown cells show a significant increase in EGF mediated EGFR activation. This promotes cell adhesion and spreading with active EGFR enriched at membrane ruffles. Both adhesion and spreading on CDMs is significantly reduced by Erlotinib treatment. Together, these findings show FBLN1C/1D, as part of the ECM, can bind and regulate EGFR activation and function in NSCLC Calu-1 cells. They further highlight the role tumor ECM composition could have in influencing EGFR dependent lung cancers.en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.subjectFBLN1en_US
dc.subjectEGFRen_US
dc.subjectECMen_US
dc.subjectCell derived matrixen_US
dc.subjectMatrix microenvironmenten_US
dc.subjectLung canceren_US
dc.subjectTOC-AUG-2020en_US
dc.subject2020en_US
dc.subject2020-AUG-WEEK2en_US
dc.titleCell Derived Matrix Fibulin-1 Associates With Epidermal Growth Factor Receptor to Inhibit Its Activation, Localization and Function in Lung Cancer Calu-1 Cellsen_US
dc.typeArticleen_US
dc.contributor.departmentDept. of Biologyen_US
dc.identifier.sourcetitleFrontiers in Cell and Developmental Biologyen_US
dc.publication.originofpublisherForeignen_US
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