收藏本站
收藏 | 手机打开
二维码
手机客户端打开本文

ΔNp63 Blocks Differentiation and Supports Cells Proliferation in Nasopharyngeal Carcinoma via Stablizing EGFR

Jing Cai  Shengnan Chen  Mei Yi  Junjun Li  Qian Peng  Wei Wang  Tan Pingqing  Guo Li  Zhaoyang Zeng  Xiaoling Li  Wei Xiong  Guiyuan Li  Bo Xiang  
【摘要】:Purpose Nasopharyngeal carcinoma(NPC) is a unique subtype of head and neck cancer rare throughout most of the world but prevalent in south China and southeast Asia. NPC is a malignancy arise from the nasopharynx stratified ciliated columnar epithelium or pseudostratified ciliated columnar epithelium, but NPC is widely regarded to be squamous in origin because of most of NPC exhibit various extent of squamous cell differentiation.That being said,the most majority of NPC cells lose columnar cell differentiation markers and express squamous cell markers. It's remain unclear how the ciliated columnar epithelium features was replaced by squamous-cell characters during NPC development. p63 is a member of the p53 family of transcription factors that plays a pivotal role in a wide range of biological processes,including stem/progenitor phenotypes, differentiation,adhesion,migration,invation,apoptosis and senescence. The ΔNp63α lacks the N-terminal transactivation domain is the predominant p63 isoform expressed in the basal and superbasal layer of nasopharynx epithelium(NPE) and overexpressed in most of NPC samples. Although the oncogenic role of ΔNp63α has been broadly reported, the role of ΔNp63α in NPC dedifferentiation is still a open question. We investigated cellular differentiation that are controlled by ΔNp63α in the basal-to-luminal switch of NPC development.Methods ΔNp63α was silenced by small interfering RNA in p63-positive NPC cells. Transcriptome profiles were performed by utilizing RNA-Seq. ChIP-Seq were performed to analyze p63 binding sites in NPC cells. The transcriptomic alteration induced by p63 silencing was compared with previous NPC transcriptome profiles(assession number GSE12452, GSE13597 and GSE15724). The effects of Np63 depletion on NPC differentiation were measured by a airliquid interface 3 D cultured assay. Cells proliferation were measured by cell growth curve, colony formation assay and cell cycle analysis. Cells migration and invasiveness were measured by wound-healing assay and transwell assays. Tumorigenicity were measured by nude mice tumor cell subcutaneous xenograft model. Proteins expression in tissue samples were detected by immunohistochemistry assay.Results In this study,we demonstrate that silecing ΔNp63α in NPC cells triggered a genes expression switch from basal to luminal type, resulting in induction of cells differentiation and reduction of cells proliferation and tumorigenicity. ChIP-Seq analysis revealed the basal-to-luminal genes expression switch triggered by ΔNp63 depletion is concomitant with genome wide H3 K4 me3, H3 K27 ace redistribution. Transcriptome profiles also revealed ΔNp63α controls near 50% differentially expressed genes during NPC development. Among these ΔNp63α promoted genes, TOP2 A, BUB1, BUB1 B, MAD2 L1, AURKA, CDC6, PCNA, CCNA2,CCNB1,CCNB2,CCND1,CDK1, and CDK4 expression were consistently reduced in ΔNp63 depletion cells, which were previously identified as hub genes during NPC development. We also demonstrated ΔNp63α maintain EGFR expression via transcriptional and post-tanslational regulation. Silencing ΔNp63α led to inhibition of EGFR transcription and triggered EGFR degradation. Immunohistochemistry assay revealed p63 protein level correlate with EGFR protein level in NPC patient samples.Conclusions Our works proved that ΔNp63α is a master factor in controlling NPC differentiation and cell proliferation. ΔNp63α could serve as a target for new therapy development.

知网文化
【相似文献】
中国期刊全文数据库 前18条
1 刘欣;毛大华;;Ki-67在Luminal型乳腺癌患者中的表达水平及其与临床病理特征的关系[J];中国老年学杂志;2017年16期
2 胡会华;周士福;;Luminal亚型乳腺癌中临床病理因子间的关系[J];四川医学;2014年04期
3 覃涛;袁中玉;彭柔君;白冰;史艳侠;滕小玉;刘冬耕;王树森;;托瑞米芬治疗Luminal型年轻乳腺癌疗效和安全性的回顾性研究[J];中山大学学报(医学科学版);2013年03期
4 崔世恩;凌飞海;储兵;;不同亚型乳腺癌初次转移时间及带瘤生存的研究[J];中华普通外科学文献(电子版);2013年04期
5 ;Breast Cancer Subtypes and Survival in Chinese Women with Operable Primary Breast Cancer[J];Chinese Journal of Cancer Research;2011年02期
6 Huafeng Kang;Zhijun Dai;Xiaobin Ma;Xing Bao;Shuai Lin;Hongbing Ma;Xiaoxu Liu;Xijing Wang;;不同分子亚型局部晚期乳腺癌的新辅化疗反应率的临床研究(英文)[J];The Chinese-German Journal of Clinical Oncology;2013年04期
7 李莎;崔福全;;TEC方案于luminal A型和luminal B型乳腺癌临床反应研究[J];齐齐哈尔医学院学报;2019年15期
8 Asmaa Salama;Habiba El-Fendy;Sahar Talaat;Badaweya Bayomi;Amr Amin;;乳腺浸润性导管癌免疫组化分层法的预后价值(英文)[J];The Chinese-German Journal of Clinical Oncology;2013年06期
9 刘佳兴;谷家梦;左怀全;;luminal A型乳腺癌患者术后预后影响因素分析[J];中华肿瘤防治杂志;2019年01期
10 陈莉颖;陈红风;付娜;叶媚娜;;218例不同分子亚型浸润性乳腺癌患者的临床特征[J];现代肿瘤医学;2007年08期
11 耿小川;华佳;庄治国;陈洁;张科蓓;张庆;成芳;;表观扩散系数直方图在新辅助化疗前预测luminal型乳腺癌疗效的价值[J];肿瘤影像学;2019年06期
12 Jiawei Wang;Chunfu Qin;Ting He;Kai Qiu;Wenjuan Sun;Xin Zhang;Ning Jiao;Weiyun Zhu;Jingdong Yin;;Alfalfa-containing diets alter luminal microbiota structure and short chain fatty acid sensing in the caecal mucosa of pigs[J];Journal of Animal Science and Biotechnology;2018年02期
13 尹喜;王成伟;张林;;Luminal型乳腺癌动态增强磁共振影像学征象分析[J];农垦医学;2017年02期
14 舒坚;;托瑞米芬和他莫昔芬治疗绝经前Luminal型乳腺癌的效果对比[J];当代医药论丛;2017年15期
15 刘国柱;王萍;辛智芳;黄丙俭;姚少波;;晚期Luminal型乳腺癌孕激素受体表达状况与化疗疗效相关性研究[J];中华肿瘤防治杂志;2020年03期
16 Ji Ma;Cheng Liu;Decao Yang;Jiagui Song;Jing Zhang;Tianzhuo Wang;Mengyuan Wang;Weizhi Xu;Xueying Li;Shigang Ding;Jun Zhan;Hongquan Zhang;;C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision[J];Science China(Life Sciences);2019年09期
17 梁越洋;唐鹏;王姝姝;张毅;;乳腺癌新辅助化疗疗效与分子分型的关系[J];中国普外基础与临床杂志;2014年05期
18 薛国军;张艳利;杨光伦;;外周血NLR和PLR预测非luminal型乳腺癌新辅助化疗临床进展的应用[J];现代医药卫生;2019年17期
中国重要会议论文全文数据库 前10条
1 Jing Cai;Shengnan Chen;Mei Yi;Junjun Li;Qian Peng;Wei Wang;Tan Pingqing;Guo Li;Zhaoyang Zeng;Xiaoling Li;Wei Xiong;Guiyuan Li;Bo Xiang;;ΔNp63 Blocks Differentiation and Supports Cells Proliferation in Nasopharyngeal Carcinoma via Stablizing EGFR[A];2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛论文汇编[C];2017年
2 Peng Wang;Jingzhi Li;Jiahui Tao;Bingdong Sha;;The crystal structure of PERK luminal domain complexed with the peptide substrate suggests the ligand-driven model for ER stress activation[A];中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议摘要集[C];2018年
3 Jiang Leiming;Yu Xuexin;姜伟;;Identification of transcription factor-miRNA-lncRNA feed-forward loops in breast cancer subtypes[A];中国生物工程学会第二届青年科技论坛暨首届青年工作委员会学术年会论文集[C];2017年
4 刘卉;;Conventional US and two-dimensional shear wave elastography(2D-SWE)of virtual touch tissue imaging quantification(VTIQ):Correlation with Immunohistochemical Subtypes of Breast Cancer[A];中国超声医学工程学会第十届全国超声治疗及生物效应医学学术大会论文汇编[C];2019年
5 董波;Shigeo Hayashi;;Endocytotic sorting and trafficking control epithelial tube geometry in Drosophila[A];细胞—生命的基础——中国细胞生物学学会2013年全国学术大会·武汉论文摘要集[C];2013年
6 刘莎;陆永奎;;对比卡培他滨和内分泌药物维持治疗Luminal型转移性乳腺癌的观察研究[A];第八届中国肿瘤学术大会暨第十三届海峡两岸肿瘤学术会议论文汇编[C];2014年
7 覃涛;袁中玉;徐菲;秦歌;杨燕华;廖玉婷;王树森;;AP2β在Luminal型乳腺癌中的表达及预后相关分析[A];中国肿瘤内科进展 中国肿瘤医师教育(2014)[C];2014年
8 覃涛;袁中玉;徐菲;杨燕华;廖玉婷;秦歌;王树森;;CPSF4在Luminal型乳腺癌中的表达及预后相关分析[A];中国肿瘤内科进展 中国肿瘤医师教育(2014)[C];2014年
9 ;Application of Serum Protein Fingerprint in Diagnosis of Coronary Artery Disease[A];2009年浙江省心电生理与起搏学术年会增刊[C];2009年
10 覃涛;秦歌;杨燕华;廖玉婷;兰琳;王树森;;CA15-3在托瑞米芬治疗的可手术Luminal型乳腺癌的预后作用[A];中国肿瘤内科进展 中国肿瘤医师教育(2014)[C];2014年
中国博士学位论文全文数据库 前4条
1 岳健;卡培他滨治疗转移性乳腺癌的药物遗传学研究以及Luminal型乳腺癌首发肝转移的临床研究[D];北京协和医学院;2014年
2 黄督平;MLF1IP在Luminal型乳腺癌中的表达及其对他莫昔芬敏感性的影响[D];南方医科大学;2017年
3 张慧明;ER-α,ER-β1,ER-β2在浸润性Luminal亚型乳腺癌中的表达分析和临床预后关系的研究[D];中国协和医科大学;2010年
4 刘婷;慢病毒介导的shRNA沉默CD151对Luminal和Basal-like型乳腺癌细胞生物学行为的影响及相关调控机制的研究[D];吉林大学;2015年
中国硕士学位论文全文数据库 前10条
1 刘卓清;CPNE1、KCTD14和FUNDC2在luminal亚型与三阴性乳腺癌中的表达差异及临床病理意义[D];南华大学;2019年
2 薛国军;外周血NLR和PLR预测非luminal型乳腺癌新辅助化疗临床进展的应用[D];重庆医科大学;2019年
3 王世科;基于DCE-MRI的影像组学在预测乳腺癌Luminal型和非Luminal型中的价值研究[D];重庆医科大学;2019年
4 赵美琳;基于MRI影像组学对于乳腺浸润性导管癌Luminal分型预测价值的初步研究[D];昆明医科大学;2018年
5 史东剑;全身免疫-炎症指数,体重指数与Luminal型乳腺癌内分泌治疗耐药的关系[D];河北医科大学;2016年
6 顾芳英;新辅助化疗前后不同亚型乳腺癌Ki-67的表达及意义[D];中南大学;2011年
7 李学梅;p53在Luminal型乳腺癌中的表达及其意义[D];遵义医学院;2015年
8 陈雪莲;Her-2阴性Luminal型乳腺癌的复发特点及治疗策略[D];北京协和医学院;2016年
9 黄艳;CYP2D6*10基因多态性及临床病理特征与服用他莫昔芬的Luminal型乳腺癌患者术后近期转移复发的相关性研究[D];遵义医学院;2015年
10 吕荣;Luminal型乳腺癌诊治回顾分析[D];广西医科大学;2016年
 快捷付款方式  订购知网充值卡  订购热线  帮助中心
  • 400-819-9993
  • 010-62982499
  • 010-62783978