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

Autor: Ayse Gokce Keskus, S. Tunçay Çağatay, Sinem Tunçer, Ozlen Konu, Melis Çolakoğlu, Sreeparna Banerjee
Rok vydání: 2016
Předmět:
0301 basic medicine
Unclassified drug
Vimentin
Cell motility
Western blotting
Metastasis
Gene overexpression
0302 clinical medicine
Cell Movement
Arachidonate 15-Lipoxygenase
Promoter Regions
Genetic
Regulation of gene expression
integumentary system
Genetic transcription
General Medicine
Complementary DNA
Chromatin immunoprecipitation
Gene Expression Regulation
Neoplastic
Arachidonate 15 lipoxygenase
030220 oncology & carcinogenesis
Colorectal Neoplasms
Uvomorulin
Colon
Motility
RNA sequence
Biology
Histone Deacetylases
Metastasis associated antigen 1
03 medical and health sciences
Antigen
Cell Line
Tumor
medicine
Humans
DNA binding
Microarray analysis techniques
Rectum
Cell adhesion
Microarray analysis
Cell Biology
Original Articles
medicine.disease
Colorectal cancer
Molecular biology
digestive system diseases
Repressor Proteins
030104 developmental biology
Immunoglobulin enhancer binding protein
Cell culture
Metastasis potential
Cancer research
biology.protein
Trans-Activators
Protein expression
Gel mobility shift assay
Tumor antigen
Controlled study
Zdroj: Cell Proliferation
ISSN: 1365-2184
Popis: 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.
Databáze: OpenAIRE
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