GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells

CD44细胞 癌症研究 环胺 音猬因子 癌症干细胞 干细胞 刺猬 生物 膀胱癌 癌症 刺猬信号通路 癌变 胶质1 免疫学 细胞 细胞生物学 信号转导 生物化学 遗传学
作者
Chong Li,Ying Du,Zhao Yang,Luyun He,Yanying Wang,Lu Hao,Mingxia Ding,Ruping Yan,Jiansong Wang,Zusen Fan
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:76 (5): 1273-1283 被引量:74
标识
DOI:10.1158/0008-5472.can-15-2309
摘要

Abstract The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. In this study, we generated a mAb (BCMab1) against CD44+ human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1+CD44+ cell subpopulation as BCSCs with stem cell–like properties. Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1+CD44+ subpopulation and was required for BCSC self-renewal. Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1+CD44+ cells and correlated with clinicopathologic features of bladder cancers. Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. Cancer Res; 76(5); 1273–83. ©2015 AACR.

科研通智能强力驱动
Strongly Powered by AbleSci AI
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
DianaLee完成签到 ,获得积分10
1秒前
1秒前
乐乐应助心动采纳,获得10
2秒前
4秒前
xzy998应助舒适路人采纳,获得10
4秒前
尽快毕业完成签到 ,获得积分10
4秒前
明亮无颜完成签到,获得积分10
5秒前
6秒前
6秒前
6秒前
Nostalgia_9完成签到,获得积分10
6秒前
天竹子发布了新的文献求助10
7秒前
YY完成签到,获得积分10
7秒前
早点睡觉完成签到,获得积分20
9秒前
9秒前
甪用发布了新的文献求助10
9秒前
9秒前
9秒前
研友_VZG7GZ应助十亿少女梦采纳,获得10
10秒前
搜集达人应助周晏平采纳,获得10
11秒前
11秒前
彭于晏应助夕余采纳,获得20
11秒前
现代的芹完成签到 ,获得积分10
12秒前
一念初见发布了新的文献求助10
14秒前
小吕快跑发布了新的文献求助10
14秒前
东山道友完成签到 ,获得积分10
16秒前
ddd完成签到,获得积分10
18秒前
18秒前
gujianhua发布了新的文献求助20
18秒前
19秒前
南木楠完成签到,获得积分10
19秒前
WaveletZ完成签到,获得积分10
20秒前
大方大船完成签到,获得积分10
21秒前
zgt01应助可靠的中心采纳,获得10
21秒前
动漫大师发布了新的文献求助10
22秒前
丫丫完成签到 ,获得积分10
23秒前
脸小呆呆发布了新的文献求助10
23秒前
24秒前
24秒前
听春风完成签到 ,获得积分10
25秒前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
Technologies supporting mass customization of apparel: A pilot project 450
A China diary: Peking 400
Brain and Heart The Triumphs and Struggles of a Pediatric Neurosurgeon 400
Cybersecurity Blueprint – Transitioning to Tech 400
Mixing the elements of mass customisation 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 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3784418
求助须知:如何正确求助?哪些是违规求助? 3329484
关于积分的说明 10242453
捐赠科研通 3044982
什么是DOI,文献DOI怎么找? 1671481
邀请新用户注册赠送积分活动 800346
科研通“疑难数据库(出版商)”最低求助积分说明 759372