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

Objectives 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 ALOX...

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Published in:	Cell proliferation Vol. 49; no. 4; pp. 448 - 459
Main Authors:	Tunçer, S., Tunçay Çağatay, S., Keşküş, A.G., Çolakoğlu, M., Konu, Ö., Banerjee, S.
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-08-2016 John Wiley and Sons Inc
Subjects:	Arachidonate 15-Lipoxygenase - genetics Cell Line, Tumor Cell Movement Colon - metabolism Colon - pathology Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Gene Expression Regulation, Neoplastic Histone Deacetylases - genetics Humans Original Promoter Regions, Genetic Rectum - metabolism Rectum - pathology Repressor Proteins - genetics Trans-Activators
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Summary:	Objectives 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.
Bibliography:	ArticleID:CPR12267 ark:/67375/WNG-HGT1V9PJ-R istex:F31EB9A5BF89CDD753DEEDB07E5BFFAD29F19E4C ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	0960-7722 1365-2184
DOI:	10.1111/cpr.12267