CHML promotes liver cancer metastasis by facilitating Rab14 recycle

Tian-Wei Chen, Fen-Fen Yin, Yan-Mei Yuan, Dong-Xian Guan, Erbin Zhang, Feng-Kun Zhang, Hao Jiang, Ning Ma, Jing-Jing Wang, Qian-Zhi Ni, Lin Qiu, Jing Feng, Xue-Li Zhang, Ying Bao, Kang Wang, Shu-Qun Cheng, Xiao-Fan Wang, Xiang Wang (), Jing-Jing Li () and Dong Xie ()
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Tian-Wei Chen: Chinese Academy of Sciences
Fen-Fen Yin: Chinese Academy of Sciences
Yan-Mei Yuan: Chinese Academy of Sciences
Dong-Xian Guan: Chinese Academy of Sciences
Erbin Zhang: Chinese Academy of Sciences
Feng-Kun Zhang: Chinese Academy of Sciences
Hao Jiang: Chinese Academy of Sciences
Ning Ma: Chinese Academy of Sciences
Jing-Jing Wang: Chinese Academy of Sciences
Qian-Zhi Ni: Chinese Academy of Sciences
Lin Qiu: Chinese Academy of Sciences
Jing Feng: Fengxian Hospital Affiliated to Southern Medical University
Xue-Li Zhang: Fengxian Hospital Affiliated to Southern Medical University
Ying Bao: Huzhou University
Kang Wang: Second Military Medical University
Shu-Qun Cheng: Second Military Medical University
Xiao-Fan Wang: Duke University Medical Center
Xiang Wang: Huzhou University
Jing-Jing Li: Chinese Academy of Sciences
Dong Xie: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10364-0

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