Abstract

Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients. CHML promotes migration, invasion and metastasis of HCC cells, in a Rab14-dependent manner. Mechanism study reveals that CHML facilitates constant recycling of Rab14 by escorting Rab14 to the membrane. Furthermore, we identify several metastasis regulators as cargoes carried by Rab14-positive vesicles, including Mucin13 and CD44, which may contribute to metastasis-promoting effects of CHML. Altogether, our data establish CHML as a potential promoter of HCC metastasis, and the CHML-Rab14 axis may be a promising therapeutic target for HCC.

Metastasis-associated recurrence is a major cause of poor prognosis in hepatocellular carcinoma. Here, the authors show that expression of choroideremia-like (CHML) is elevated and associates with poor prognosis in hepatocellular carcinoma, and mechanistically CHML promotes metastasis in a Rab14-dependent manner.

Details

Title
CHML promotes liver cancer metastasis by facilitating Rab14 recycle
Author
Tian-Wei, Chen 1 ; Yin Fen-Fen 2 ; Yan-Mei, Yuan 2 ; Dong-Xian, Guan 3 ; Zhang Erbin 2 ; Feng-Kun, Zhang 2 ; Jiang, Hao 2 ; Ma, Ning 2 ; Jing-Jing, Wang 3 ; Qian-Zhi, Ni 2 ; Qiu, Lin 3 ; Feng, Jing 4 ; Xue-Li, Zhang 4 ; Bao, Ying 5 ; Wang, Kang 6 ; Cheng Shu-Qun 6 ; Xiao-Fan, Wang 7 ; Wang, Xiang 8 ; Jing-Jing, Li 2 ; Xie, Dong 9 

 Chinese Academy of Sciences, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309); Chinese Academy of Sciences, University of Chinese Academy of Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309); Fengxian Hospital Affiliated to Southern Medical University, Department of General Surgery, Shanghai, China (GRID:grid.9227.e) 
 Chinese Academy of Sciences, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309); Chinese Academy of Sciences, University of Chinese Academy of Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
 Chinese Academy of Sciences, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
 Fengxian Hospital Affiliated to Southern Medical University, Department of General Surgery, Shanghai, China (GRID:grid.9227.e) 
 Huzhou University, Department of Surgery, First People’s Hospital Affiliated, Huzhou, China (GRID:grid.411440.4) (ISNI:0000 0001 0238 8414) 
 Second Military Medical University, Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China (GRID:grid.73113.37) (ISNI:0000 0004 0369 1660) 
 Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
 Huzhou University, Key Laboratory for Translational Medicine, First People’s Hospital Affiliated, Huzhou, China (GRID:grid.411440.4) (ISNI:0000 0001 0238 8414) 
 Chinese Academy of Sciences, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309); Chinese Academy of Sciences, University of Chinese Academy of Sciences, Xuhui district, China (GRID:grid.9227.e) (ISNI:0000000119573309); China National Center for Food Safety Risk Assessment, NHC Key Laboratory of Food Safety Risk Assessment, Beijing, China (GRID:grid.464207.3) (ISNI:0000 0004 4914 5614); ShanghaiTech University, School of Life Science and Technology, Shanghai, China (GRID:grid.440637.2) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2236685961
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.