Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

作     者：Qian Liu Junwen Zhang Hua Gao Taoyang Yuan Jie Kang Lu Jin Songbai Gui Yazhuo Zhang 

作者机构：Beijing Neurosurgical Institute Capital Medical University Key Laboratory of Central Nervous System Injury Research Beijing Institute for Brain Disorders Brain Tumor Center China National Clinical Research Center for Neurological Diseases Capital Medical University Beijing Tiantan Hospital Capital Medical University 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2018年第61卷第8期

页      面：893-901页

核心收录：

学科分类：0710[理学-生物学] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (81502154) Research Special Fund For Public Welfare Industry of Health of China (201402008) National High Technology Research and Development Program of China (2015AA020504) 

主　　题：EGFL7 EGFR growth hormone-producing pituitary adenomas (GHPA) invasion tumorigenesis 

摘      要：Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas （GHPA） is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7 （EGFL7） is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPA was much higher than that ofnon-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR （p-EGFR）. Noticeably, EGFL7 knockdown sig- nificantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GTI-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.