A Novel EGFR Isoform Confers Increased Invasiveness to Cancer Cells

被引：25

作者：

Zhou, Min ^{[1
]}

Wang, Hai ^{[1
]}

Zhou, Keke ^{[2
]}

Luo, Xiaoying ^{[1
]}

Pan, Xiaorong ^{[1
]}

Shi, Bizhi ^{[1
]}

Jiang, Hua ^{[1
]}

Zhang, Jiqin ^{[1
]}

Li, Kesang ^{[1
]}

Wang, Hua-Mao ^{[1
]}

Gao, Huiping ^{[1
]}

Lu, Shun ^{[3
]}

Yao, Ming ^{[1
]}

Mao, Ying ^{[2
]}

Wang, Hong-Yang ^{[1
,4
]}

Yang, Shengli ^{[1
]}

Gu, Jianren ^{[1
]}

Li, Chuanyuan ^{[5
]}

Li, Zonghai ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Renji Hosp, Shanghai Canc Inst,Sch Med, Shanghai 200032, Peoples R China

[2] Fudan Univ, Dept Neurosurg, Huashan Hosp, Shanghai 200433, Peoples R China

[3] Shanghai Jiao Tong Univ, Chest Hosp, Shanghai Lung Tumor Clin Med Ctr, Shanghai 200032, Peoples R China

[4] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Signal Transduct, Shanghai, Peoples R China

[5] Duke Univ, Med Ctr, Dept Dermatol, Durham, NC USA

来源：

CANCER RESEARCH | 2013年 / 73卷 / 23期

基金：

中国国家自然科学基金;

关键词：

GROWTH-FACTOR RECEPTOR; COLORECTAL-CANCER; LUNG-CANCER; EXPRESSION; PROGNOSIS; TRANSCRIPTION; METASTASIS; ACTIVATION; THERAPY; GLIOMAS;

D O I：

10.1158/0008-5472.CAN-13-0194

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform termed EGFRvA, which substitutes a Ser/Thr-rich peptide for part of the carboxyl-terminal regulatory domain of the receptor. Intriguingly, EGFRvA expression relates more closely to histopathologic grade and poor prognosis in patients with glioma. Ectopic expression of EGFRvA in cancer cells conferred a higher invasive capacity than EGFR in vitro and in vivo. Mechanistically, EGFRvA stimulated expression of STAT3, which upregulated heparin-binding EGF (HB-EGF). Reciprocally, HB-EGF stimulated phosphorylation of EGFRvA at Y845 along with STAT3, generating a positive feedback loop that may reinforce invasive function. The significance of EGFRvA expression was reinforced by findings that it is attenuated by miR-542-5p, a microRNA that is a known tumor suppressor. Taken together, our findings define this newfound EGFR isoform as a key theranostic molecule. (C)2013 AACR.

引用

页码：7056 / 7067

页数：12

共 40 条

[1] c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function [J].