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dc.contributor.authorLeiser, Dominic
dc.contributor.authorSamanta, Santanu
dc.contributor.authorEley, John
dc.contributor.authorStrauss, Josh
dc.contributor.authorCreed, Michael
dc.contributor.authorKingsbury, Tami
dc.contributor.authorStaats, Paul N
dc.contributor.authorBhandary, Binny
dc.contributor.authorChen, Minjie
dc.contributor.authorDukic, Tijana
dc.contributor.authorRoy, Sanjit
dc.contributor.authorMahmood, Javed
dc.contributor.authorVujaskovic, Zeljko
dc.contributor.authorShukla, Hem D
dc.date.accessioned2021-11-18T18:00:16Z
dc.date.available2021-11-18T18:00:16Z
dc.date.issued2021-11-11
dc.identifier.urihttp://hdl.handle.net/10713/17148
dc.description.abstractRadiation therapy plays a major role in the treatment of lung cancer patients. However, cancer cells develop resistance to radiation. Tumor radioresistance is a complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, and the clonal selection of radioresistant cells from the heterogeneous tumor site, and it is a major cause of treatment failure in non-small cell lung cancer (NSCLC). In the present investigation caveolin-1 (CAV-1) has been observed to be highly expressed in radiation resistant A549 lung cancer cells. CRISPR-Cas9 knockout of CAV-1 reverted the cells to a radio sensitive phenotype. In addition, CAV-1 overexpression in parental A549 cells, led to radiation resistance. Further, gene expression analysis of A549 parental, radiation resistant, and caveolin-1 overexpressed cells, exhibited overexpression of DNA repair genes RAD51B, RAD18, SOX2 cancer stem cell marker, MMPs, mucins and cytoskeleton proteins in resistant and caveolin-1 over expressed A549 cells, as compared to parental A549 cells. Bioinformatic analysis shows upregulation of BRCA1, Nuclear Excision DNA repair, TGFB and JAK/STAT signaling pathways in radioresistant and caveolin-1 overexpressed cells, which may functionally mediate radiation resistance. Immunohistochemistry data demonstrated heterogeneous expression of CAV-1 gene in human lung cancer tissues, which was analogous to its enhanced expression in human lung cancer cell line model and mouse orthotopic xenograft lung cancer model. Also, TCGA PanCancer clinical studies have demonstrated amplification, deletions and missense mutation in CAV-1 gene in lung cancer patients, and that CAV-1 alteration has been linked to poor prognosis, and poor survival in lung cancer patients. Interestingly, we have also optimized ELISA assay to measure caveolin-1 protein in the blood of A549 radiation resistant human xenograft preclinical mouse model and discovered higher level of caveolin-1 (950 pg/ml) in tumor bearing animals treated with radiation, as compared to xenograft with radiosensitive lung cancer cells (450 pg/ml). Thus, we conclude that caveolin-1 is involved in radio-resistance and contributes to tumor aggression, and it has potential to be used as prognostic biomarker for radiation treatment response, and tumor progression for precision medicine in lung cancer patients.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0258951en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONEen_US
dc.subject.meshBiomarkers, Tumoren_US
dc.subject.meshCarcinoma, Non-Small-Cell Lungen_US
dc.subject.meshCaveolin 1en_US
dc.subject.meshRadiation Toleranceen_US
dc.titleRole of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung canceren_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0258951
dc.identifier.pmid34762666
dc.source.volume16
dc.source.issue11
dc.source.beginpagee0258951
dc.source.endpage
dc.source.countryUnited States


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