亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Cervical Cancer Stem Cells Selectively Overexpress HPV Oncoprotein E6 that Controls Stemness and Self-Renewal through Upregulation of HES1

SOX2 赫斯1 干细胞 癌症干细胞 生物 同源盒蛋白纳米 癌症研究 干细胞标记物 癌变 细胞分化 细胞生物学 癌症 Notch信号通路 胚胎干细胞 信号转导 诱导多能干细胞 遗传学 基因
作者
Abhishek Tyagi,Kanchan Vishnoi,Sutapa Mahata,G. S. Verma,Yogesh Srivastava,Shashank Masaldan,Bal Gangadhar Roy,Alok C. Bharti,Bhudev C. Das
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:22 (16): 4170-4184 被引量:66
标识
DOI:10.1158/1078-0432.ccr-15-2574
摘要

Abstract Purpose: Perturbation of keratinocyte differentiation by E6/E7 oncoproteins of high-risk human papillomaviruses that drive oncogenic transformation of cells in squamocolumnar junction of the uterine cervix may confer “stem-cell like” characteristics. However, the crosstalk between E6/E7 and stem cell signaling during cervical carcinogenesis is not well understood. We therefore examined the role of viral oncoproteins in stem cell signaling and maintenance of stemness in cervical cancer. Experimental Design: Isolation and enrichment of cervical cancer stem–like cells (CaCxSLCs) was done from cervical primary tumors and cancer cell lines by novel sequential gating using a set of functional and phenotypic markers (ABCG2, CD49f, CD71, CD133) in defined conditioned media for assessing sphere formation and expression of self-renewal and stemness markers by FACS, confocal microscopy, and qRT-PCR. Differential expression level and DNA-binding activity of Notch1 and its downstream targets in CaCxSLCs as well as silencing of HPVE6/Hes1 by siRNA was evaluated by gel retardation assay, FACS, immunoblotting, and qRT-PCR followed by in silico and in vivo xenograft analysis. Results: CaCxSLCs showed spheroid-forming ability, expressed self-renewal and stemness markers Oct4, Sox2, Nanog, Lrig1, and CD133, and selectively overexpressed E6 and HES1 transcripts in both cervical primary tumors and cancer cell lines. The enriched CaCxSLCs were highly tumorigenic and did recapitulate primary tumor histology in nude mice. siRNA silencing of HPVE6 or Hes1 abolished sphere formation, downregulated AP-1-STAT3 signaling, and induced redifferentiation. Conclusions: Our findings suggest the possible mechanism by which HPVE6 potentially regulate and maintain stem-like cancer cells through Hes1. Clin Cancer Res; 22(16); 4170–84. ©2016 AACR.
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

祝大家在新的一年里科研腾飞
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
3秒前
张寒发布了新的文献求助10
10秒前
科研通AI2S应助科研通管家采纳,获得10
11秒前
jyy应助科研通管家采纳,获得10
11秒前
张寒完成签到,获得积分10
14秒前
Zhouzhou完成签到,获得积分10
18秒前
18秒前
Zhouzhou发布了新的文献求助10
21秒前
grisco完成签到,获得积分10
21秒前
36秒前
38秒前
Owen应助Zhouzhou采纳,获得10
39秒前
大个应助高兴的彩虹采纳,获得10
41秒前
42秒前
tarako发布了新的文献求助10
47秒前
稻子完成签到 ,获得积分10
51秒前
55秒前
共享精神应助tarako采纳,获得10
59秒前
Jenny发布了新的文献求助10
1分钟前
1分钟前
Jenny完成签到,获得积分10
1分钟前
楠茸完成签到 ,获得积分10
1分钟前
JamesPei应助我要帅个够采纳,获得10
1分钟前
1分钟前
1分钟前
1分钟前
1分钟前
1分钟前
qwertyui发布了新的文献求助10
1分钟前
wpj发布了新的文献求助10
1分钟前
1分钟前
Orange应助wpj采纳,获得10
1分钟前
rnf发布了新的文献求助10
1分钟前
1分钟前
1分钟前
等待的剑身完成签到,获得积分10
1分钟前
rnf完成签到,获得积分10
1分钟前
三更笔舞发布了新的文献求助10
1分钟前
1分钟前
1分钟前
高分求助中
Востребованный временем 2500
The Three Stars Each: The Astrolabes and Related Texts 1500
Les Mantodea de Guyane 1000
Very-high-order BVD Schemes Using β-variable THINC Method 970
Field Guide to Insects of South Africa 660
Foucault's Technologies Another Way of Cutting Reality 500
Forensic Chemistry 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3392915
求助须知:如何正确求助?哪些是违规求助? 3003337
关于积分的说明 8808873
捐赠科研通 2690142
什么是DOI,文献DOI怎么找? 1473469
科研通“疑难数据库(出版商)”最低求助积分说明 681591
邀请新用户注册赠送积分活动 674515