文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

表皮生长因子受体（EGFR）及其突变体 EGFRvIII 与 PUMA 相互作用，抑制 PUMA 的线粒体易位和 EGFR 激酶活性不依赖的 PUMA 介导线粒体凋亡。

EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity.

机构信息

Department of Surgery, Divisions of Surgical Sciences and Neurosurgery, Duke University School of Medicine, 103 Research Drive, Durham, NC 27710, USA.

出版信息

Cancer Lett. 2010 Aug 1;294(1):101-10. doi: 10.1016/j.canlet.2010.01.028. Epub 2010 Feb 13.

DOI:10.1016/j.canlet.2010.01.028
PMID:20153921
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2875288/
Abstract

EGFR and its constitutively activated variant EGFRvIII are linked to glioblastoma resistance to therapy, the mechanisms underlying this association, however, are still unclear. We report that in glioblastoma, EGFR/EGFRvIII paradoxically co-expresses with p53-upregulated modulator of apoptosis (PUMA), a proapoptotic member of the Bcl-2 family of proteins primarily located on the mitochondria. EGFR/EGFRvIII binds to PUMA constitutively and under apoptotic stress, and subsequently sequesters PUMA in the cytoplasm. The EGFR-PUMA interaction is independent of EGFR activation and is sustained under EGFR inhibition. A Bcl-2/Bcl-xL inhibitor that mimics PUMA activity sensitizes EGFR/EGFRvIII-expressing glioblastoma cells to Iressa. Collectively, we uncovered a novel kinase-independent function of EGFR/EGFRvIII that leads to tumor drug resistance.

摘要

表皮生长因子受体（EGFR）及其组成性激活变体 EGFRvIII 与胶质母细胞瘤对治疗的耐药性有关，但这一关联的机制尚不清楚。我们报告称，在胶质母细胞瘤中，EGFR/EGFRvIII 与 p53 上调的凋亡调节剂（PUMA）反常共表达，后者是 Bcl-2 蛋白家族的一种促凋亡成员，主要位于线粒体上。EGFR/EGFRvIII 与 PUMA 持续结合，在凋亡应激下，随后将 PUMA 隔离在细胞质中。EGFR-PUMA 相互作用不依赖于 EGFR 的激活，并在 EGFR 抑制下持续存在。一种模拟 PUMA 活性的 Bcl-2/Bcl-xL 抑制剂可使表达 EGFR/EGFRvIII 的胶质母细胞瘤细胞对易瑞沙敏感。总的来说，我们揭示了 EGFR/EGFRvIII 的一种新的非激酶依赖的功能，导致肿瘤耐药。

相似文献

[1]
EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity.

Cancer Lett. 2010-2-13

[2]
Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme.

Clin Cancer Res. 2004-5-1

[3]
PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells.

Oncogene. 2009-6-18

[4]
EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: a potential mechanism of EGFR-driven antagonism of apoptosis.

Mol Cancer. 2011-3-9

[5]
Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with upregulation of EGFRvIII and PI3Kp110δ.

Neuro Oncol. 2013-7-21

[6]
Chronic activation of wild-type epidermal growth factor receptor and loss of Cdkn2a cause mouse glioblastoma formation.

Cancer Res. 2011-10-10

[7]
EGFRvIII Confers Sensitivity to Saracatinib in a STAT5-Dependent Manner in Glioblastoma.

Int J Mol Sci. 2024-6-6

[8]
Crosstalk between the urokinase-type plasminogen activator receptor and EGF receptor variant III supports survival and growth of glioblastoma cells.

Proc Natl Acad Sci U S A. 2011-9-6

[9]
Lovastatin enhances gefitinib activity in glioblastoma cells irrespective of EGFRvIII and PTEN status.

J Neurooncol. 2008-10

[10]
PUMA and BIM are required for oncogene inactivation-induced apoptosis.

Sci Signal. 2013-3-26

引用本文的文献

[1]
A PROTAC degrader suppresses oncogenic functions of PTK6, inducing apoptosis of breast cancer cells.

Cell Chem Biol. 2025-2-20

[2]
OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1.

Biomolecules. 2023-6-16

[3]
Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.

Pharmacol Rev. 2023-11

[4]
N6-Isopentenyladenosine Impairs Mitochondrial Metabolism through Inhibition of EGFR Translocation on Mitochondria in Glioblastoma Cells.

Cancers (Basel). 2022-12-8

[5]
Fluorescence Imaging of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer.

Cancers (Basel). 2022-1-28

[6]
Novel Tyrosine Kinase Targets in Urothelial Carcinoma.

Int J Mol Sci. 2021-1-13

[7]
Rethink of EGFR in Cancer With Its Kinase Independent Function on Board.

Front Oncol. 2019-8-23

[8]
Kinase-Inactivated EGFR Is Required for the Survival of Wild-Type EGFR-Expressing Cancer Cells Treated with Tyrosine Kinase Inhibitors.

Int J Mol Sci. 2019-5-22

[9]
Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.

J Neurooncol. 2018-3-21

[10]
FHL2 interacts with EGFR to promote glioblastoma growth.

Oncogene. 2018-1-11

本文引用的文献

[1]
Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes.

Mol Cancer Res. 2010-2-9

[2]
EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance.

Curr Mol Pharmacol. 2010-1

[3]
A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion.

Cancer Res. 2009-9-1

[4]
Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor.

Cancer Res. 2009-8-1

[5]
Apoptosis and cancer: the genesis of a research field.

Nat Rev Cancer. 2009-7

[6]
Plasminogen kringle 5 induces apoptosis of brain microvessel endothelial cells: sensitization by radiation and requirement for GRP78 and LRP1.

Cancer Res. 2009-7-1

[7]
PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells.

Oncogene. 2009-6-18

[8]
Tyrosine phosphorylation of the human glutathione S-transferase P1 by epidermal growth factor receptor.

J Biol Chem. 2009-6-19

[9]
Stem cells for treating glioblastoma: how close to reality?

Neuro Oncol. 2009-4

[10]
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.

Neuro Oncol. 2009-10

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索