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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.
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1 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)
2 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)
3 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)
4 Fengxian Hospital Affiliated to Southern Medical University, Department of General Surgery, Shanghai, China (GRID:grid.9227.e)
5 Huzhou University, Department of Surgery, First People’s Hospital Affiliated, Huzhou, China (GRID:grid.411440.4) (ISNI:0000 0001 0238 8414)
6 Second Military Medical University, Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China (GRID:grid.73113.37) (ISNI:0000 0004 0369 1660)
7 Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216)
8 Huzhou University, Key Laboratory for Translational Medicine, First People’s Hospital Affiliated, Huzhou, China (GRID:grid.411440.4) (ISNI:0000 0001 0238 8414)
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); 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)