Open AccessInterplay between 15‐lipoxygenase‐1 and metastasis‐associated antigen 1 in the metastatic potential of colorectal cancer
Author(s) -
Tunçer S.,
Tunçay Çağatay S.,
Keşküş A.G.,
Çolakoğlu M.,
Konu Ö.,
Banerjee S.
Publication year - 2016
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12267
Subject(s) - metastasis , biology , cancer research , colorectal cancer , chromatin immunoprecipitation , cell culture , microarray analysis techniques , cell adhesion , microbiology and biotechnology , motility , cancer , promoter , gene expression , cell , gene , genetics
Objectives Metastasis‐associated antigen 1 ( MTA 1) 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 MTA 1 and 15‐ LOX ‐1 in CRC metastasis. Materials and methods ALOX 15 and MTA 1 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 (Ch IP ), 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; MTA 1 overexpression resulted in reduced adhesion in CRC cell lines. Re‐expression of 15‐ LOX ‐1 in the CRC cell lines reduced expression of endogenous MTA 1, 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 MTA 1 promoter was significantly lower in cells re‐expressing 15‐ LOX ‐1. Functionally, the same cells had reduced motility, which was rescued when they overexpressed MTA 1, and further corroborated by expressions of E‐cadherin and vimentin. Conclusions Expression of MTA 1 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 MTA 1 promoter.