Interplay between 15-lipoxygenase-1 and metastasisassociated antigen 1 in the metastatic potential of colorectal cancer

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dc.citation.epage459en_US
dc.citation.issueNumber4en_US
dc.citation.spage448en_US
dc.citation.volumeNumber49en_US
dc.contributor.authorTunçer, S.en_US
dc.contributor.authorÇağatay, T. S.en_US
dc.contributor.authorKeşküş, A. G.en_US
dc.contributor.authorÇolakoğlu, M.en_US
dc.contributor.authorKonu, Ö.en_US
dc.contributor.authorBanerjee S.en_US
dc.date.accessioned2018-04-12T10:39:19Z
dc.date.available2018-04-12T10:39:19Z
dc.date.issued2016en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractObjectives: Metastasis-associated antigen 1 (MTA1) is implicated in metastasis while 15-lipoxygenase-1 (15-LOX-1) reduces cell motility, when re-expressed in colorectal cancer (CRC). We aimed to understand any potential interplay between MTA1 and 15-LOX-1 in CRC metastasis. Materials and methods: ALOX15 and MTA1 expression in tumour and normal samples were analysed from TCGA RNA-seq data, microarray data sets and a human CRC cDNA array. Western blots, chromatin immunoprecipitation (ChIP), luciferase assays and electrophoretic mobility shift assays (EMSA) were carried out in HT-29 and LoVo cells re-expressing 15-LOX-1 to determine NF- κB activity at the MTA1 promoter. Functional assays in cells ectopically expressing either 15-LOX-1, MTA-1 or both, were carried out to determine adhesion and cell motility. Results: Significantly higher expression of MTA1 was observed in tumours compared to normal tissues; MTA1 overexpression resulted in reduced adhesion in CRC cell lines. Re-expression of 15-LOX-1 in the CRC cell lines reduced expression of endogenous MTA1, corroborated by negative correlation between the two genes in two independent human CRC microarray data sets, with greater significance in specific subsets of patients. DNA binding and transcriptional activity of NF-κB at the MTA1 promoter was significantly lower in cells re-expressing 15-LOX-1. Functionally, the same cells had reduced motility, which was rescued when they overexpressed MTA1, and further corroborated by expressions of E-cadherin and vimentin. Conclusions: Expression of MTA1 and 15-LOX-1 negatively correlated in specific subsets of CRC. Mechanistically, this is at least in part through reduced recruitment of NF-κB to the MTA1 promoter.en_US
dc.identifier.doi10.1111/cpr.12267en_US
dc.identifier.eissn1365-2184
dc.identifier.issn0960-7722
dc.identifier.urihttp://hdl.handle.net/11693/36422
dc.language.isoEnglishen_US
dc.publisherWiley-Blackwell Publishing Ltd.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1111/cpr.12267en_US
dc.source.titleCell Proliferationen_US
dc.subjectArachidonate 15 lipoxygenaseen_US
dc.subjectComplementary DNAen_US
dc.subjectImmunoglobulin enhancer binding proteinen_US
dc.subjectMetastasis associated antigen 1en_US
dc.subjectTumor antigenen_US
dc.subjectUnclassified drugen_US
dc.subjectUvomorulinen_US
dc.subjectVimentinen_US
dc.subjectCell adhesionen_US
dc.subjectCell motilityen_US
dc.subjectChromatin immunoprecipitationen_US
dc.subjectColorectal canceren_US
dc.subjectControlled studyen_US
dc.subjectDNA bindingen_US
dc.subjectGel mobility shift assayen_US
dc.subjectGene overexpressionen_US
dc.subjectGenetic transcriptionen_US
dc.subjectMetastasis potentialen_US
dc.subjectMicroarray analysisen_US
dc.subjectProtein expressionen_US
dc.subjectRNA sequenceen_US
dc.subjectWestern blottingen_US
dc.titleInterplay between 15-lipoxygenase-1 and metastasisassociated antigen 1 in the metastatic potential of colorectal canceren_US
dc.typeArticleen_US

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