A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression

内吞作用 癌症研究 受体 受体酪氨酸激酶 内体 医学 细胞凋亡 细胞生物学 生物 化学 内科学 生物化学
作者
Ashley E. Pall,Lena Juratli,Dhyana Guntur,K. Bandyopadhyay,Kalyan C. Kondapalli
出处
期刊:Journal of Cellular and Molecular Medicine [Wiley]
卷期号:23 (11): 7859-7872 被引量:10
标识
DOI:10.1111/jcmm.14665
摘要

Abstract Glioblastoma (GBM) is the most frequent and inevitably lethal primary brain cancer in adults. It is recognized that the overexpression of the endosomal Na + /H + exchanger NHE9 is a potent driver of GBM progression. Patients with NHE9 overexpression have a threefold lower median survival relative to GBM patients with normal NHE9 expression, using available treatment options. New treatment strategies tailored for this GBM subset are much needed. According to the prevailing model, NHE9 overexpression leads to an increase in plasma membrane density of epidermal growth factor receptors (EGFRs) which consequently enhances GBM cell proliferation and migration. However, this increase is not specific to EGFRs. In fact, the hallmark of NHE9 overexpression is a pan‐specific increase in plasma membrane receptors. Paradoxically, we report that this gain of function in NHE9 can be exploited to effectively target GBM cells for destruction. When exposed to gold nanoparticles, NHE9 overexpressing GBM cells accumulated drastically high amounts of gold via receptor‐mediated endocytosis, relative to control. Irradiation of these cells with near‐infrared light led to apoptotic tumour cell death. A major limitation for delivering therapeutics to GBM cells is the blood‐brain barrier (BBB). Here, we demonstrate that macrophages loaded with gold nanoparticles can cross the BBB, deliver the gold nanoparticles and effect the demise of GBM cells. In combination with receptor tyrosine kinase inhibition, we show this approach holds great promise for a new GBM‐targeted therapy.
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
恋雅颖月应助乐观的寻绿采纳,获得10
刚刚
Shrine完成签到,获得积分10
刚刚
英姑应助紫色奶萨采纳,获得10
2秒前
3秒前
4秒前
希望天下0贩的0应助Jay采纳,获得10
5秒前
5秒前
爆米花应助zewangguo采纳,获得10
6秒前
斯文败类应助loong采纳,获得10
7秒前
深情安青应助Xin采纳,获得10
8秒前
和花花发布了新的文献求助10
8秒前
摩卡完成签到,获得积分10
9秒前
10秒前
11秒前
端庄毛巾完成签到,获得积分10
11秒前
12秒前
12秒前
12秒前
张雯思发布了新的文献求助10
14秒前
ding应助Nugget采纳,获得10
14秒前
幸福大白发布了新的文献求助30
17秒前
wdy111举报ZZZ求助涉嫌违规
18秒前
zewangguo发布了新的文献求助10
18秒前
19秒前
高大的冰双完成签到,获得积分10
20秒前
22秒前
987完成签到 ,获得积分10
23秒前
loong完成签到,获得积分10
23秒前
紫色奶萨发布了新的文献求助10
24秒前
zewangguo完成签到,获得积分10
24秒前
25秒前
如意手链完成签到,获得积分10
26秒前
DongWei95发布了新的文献求助30
27秒前
锦诗完成签到,获得积分10
28秒前
isojso发布了新的文献求助10
29秒前
30秒前
科研通AI2S应助科研通管家采纳,获得10
34秒前
共享精神应助科研通管家采纳,获得10
34秒前
搜集达人应助科研通管家采纳,获得10
34秒前
tramp应助科研通管家采纳,获得10
34秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3989406
求助须知:如何正确求助?哪些是违规求助? 3531522
关于积分的说明 11254187
捐赠科研通 3270174
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174