GOLM1 Modulates EGFR/RTK Cell-Surface Recycling to Drive Hepatocellular Carcinoma Metastasis

被引:194
作者
Ye, Qing-Hai [1 ]
Zhu, Wen-Wei [1 ,2 ]
Zhang, Ju-Bo [1 ,8 ]
Qin, Yi [3 ,7 ]
Lu, Ming [2 ]
Lin, Guo-Ling [1 ]
Guo, Lei [1 ]
Zhang, Bo [1 ]
Lin, Zhen-Hai [1 ]
Roessler, Stephanie [4 ,6 ]
Forgues, Marshonna [4 ]
Jia, Hu-Liang [2 ]
Lu, Lu [2 ]
Zhang, Xiao-Fei [2 ]
Lian, Bao-Feng [5 ]
Xie, Lu [5 ]
Dong, Qiong-Zhu [2 ,3 ]
Tang, Zhao-You [1 ,2 ]
Wang, Xin Wei [4 ]
Qin, Lun-Xiu [1 ,2 ,3 ]
机构
[1] Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China
[2] Fudan Univ, Canc Metastasis Inst, Huashan Hosp, Dept Gen Surg, 12 Urumqi Rd M, Shanghai 200040, Peoples R China
[3] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China
[4] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA
[5] Shanghai Ctr Bioinformat Technol, Shanghai 201203, Peoples R China
[6] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany
[7] Fudan Univ, Dept Pancreat & Hepatobiliary Surg, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
[8] Fudan Univ, Huashan Hosp, Dept Infect Dis, Shanghai 200040, Peoples R China
关键词
RECEPTOR TYROSINE KINASES; GOLGI-APPARATUS; CANCER; TRAFFICKING; INTEGRIN; ACTIVATION; GROWTH; FIBROBLASTS; ENDOCYTOSIS; INHIBITION;
D O I
10.1016/j.ccell.2016.07.017
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The mechanism of cancer metastasis remains poorly understood. Using gene profiling of hepatocellular carcinoma (HCC) tissues, we have identified GOLM1 as a leading gene relating to HCC metastasis. GOLM1 expression is correlated with early recurrence, metastasis, and poor survival of HCC patients. Both gain and loss-of-function studies determine that GOLM1 acts as a key oncogene by promoting HCC growth and metastasis. It selectively interacts with epidermal growth factor receptor (EGFR) and serves as a specific cargo adaptor to assist EGFR/RTK anchoring on the trans-Golgi network (TGN) and recycling back to the plasma membrane, leading to prolonged activation of the downstream kinases. These findings reveal the functional role of GOLM1, a Golgi-related protein, in EGFR/RTK recycling and metastatic progression of HCC.
引用
收藏
页码:444 / 458
页数:15
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