SNAI1-mediated transcriptional regulation of epithelial-to-mesenchymal transition genes in breast cancer stem cells

第1章 上皮-间质转换 癌症研究 癌症干细胞 生物 扭曲转录因子 癌变 人口 细胞迁移 细胞生物学 转移 癌症 干细胞 细胞 遗传学 医学 环境卫生
作者
Digvijay Singh,Rohit K. Deshmukh,Amitava Das
出处
期刊:Cellular Signalling [Elsevier BV]
卷期号:87: 110151-110151 被引量:22
标识
DOI:10.1016/j.cellsig.2021.110151
摘要

Triple-negative breast cancer (TNBC) tumors are composed of a heterogeneous population containing both cancer cells and cancer stem cells (CSCs). These CSCs are generated through an epithelial-to-mesenchymal transition (EMT), thus making it pertinent to identify the unique EMT-molecular targets that regulate this phenomenon.In the present study, we performed in silico analysis of microarray data from luminal, Her2+, and TNBC cell lines and identified 15 relatively unexplored EMT-related differentially expressed genes (DEGs) along with the markedly high expression of EMT-transcription factor (EMT-TF), SNAI1. Interestingly, stable overexpression of SNAI1 in MCF-7 induced the expression of DEGs along with increased migration, invasion, and in vitro tumorigenesis that was comparable to TNBCs. Next, stable SNAI1 overexpression led to increased expression of DEGs that was reverted with SNAI1 silencing in both breast cancer cells and CSCs sorted from various TNBC cell lines. Higher fold enrichment of SNAI1 on E-boxes in the promoter regions suggested a positive regulation of ALCAM, MMP2, MMP13, MMP14, VCAN, ANKRD1, KRT16, CTGF, TGFRIIβ, PROCR negative regulation of CDH1, DSP and DSC3B by SNAI1 leading to EMT. Furthermore, SNAI1-mediated increased migration, invasion, and tumorigenesis in these sorted cells led to the activation of signaling mediators, ERK1/2, STAT3, Src, and FAK. Finally, the SNAI1-mediated activation of breast CSC phenotypes was perturbed by inhibition of downstream target, MMPs using Ilomastat.Thus, the molecular investigation for the gene regulatory framework in the present study identified MMPs, a downstream effector in the SNAI1-mediated EMT regulation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
1秒前
3秒前
pengjiejie发布了新的文献求助10
4秒前
MW完成签到,获得积分10
4秒前
xiaomi完成签到,获得积分10
5秒前
支半雪发布了新的文献求助10
5秒前
6秒前
7秒前
7秒前
毕业比耶发布了新的文献求助10
8秒前
着急的cc完成签到,获得积分10
8秒前
9秒前
30888136发布了新的文献求助10
10秒前
11秒前
希望天下0贩的0应助bruce233采纳,获得10
11秒前
www完成签到 ,获得积分10
11秒前
Jasper应助Leon_nomoreLess采纳,获得10
13秒前
Yumori关注了科研通微信公众号
13秒前
Hello应助33采纳,获得10
13秒前
许鹤缤发布了新的文献求助10
13秒前
郭小燕发布了新的文献求助10
14秒前
hanch完成签到,获得积分10
14秒前
量子星尘发布了新的文献求助10
16秒前
17秒前
18秒前
务实发夹完成签到,获得积分10
18秒前
18秒前
周少发布了新的社区帖子
18秒前
智博36完成签到,获得积分10
20秒前
21秒前
醋溜滑板完成签到 ,获得积分10
21秒前
在水一方应助钱钱钱采纳,获得10
21秒前
Yumori发布了新的文献求助10
23秒前
23秒前
耿教授发布了新的文献求助10
23秒前
sb发布了新的文献求助10
23秒前
小娄发布了新的文献求助10
25秒前
25秒前
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Effective Learning and Mental Wellbeing 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975922
求助须知:如何正确求助?哪些是违规求助? 3520226
关于积分的说明 11201711
捐赠科研通 3256720
什么是DOI,文献DOI怎么找? 1798423
邀请新用户注册赠送积分活动 877576
科研通“疑难数据库(出版商)”最低求助积分说明 806452