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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / secondary
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HEK293 Cells
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Humans
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Hyaluronan Receptors / metabolism
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Liver Neoplasms / genetics*
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Lung Neoplasms / metabolism
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Lung Neoplasms / secondary
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Mice
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Mice, Nude
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Mucins / metabolism
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Neoplasm Invasiveness
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Neoplasm Recurrence, Local / genetics
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Neoplasm Recurrence, Local / metabolism
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Neoplasm Transplantation
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Neoplasms, Multiple Primary / metabolism*
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Neoplasms, Multiple Primary / pathology
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RNA, Messenger / metabolism
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Tumor Burden
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rab GTP-Binding Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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CD44 protein, human
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CHML protein, human
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Hyaluronan Receptors
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MUC13 protein, human
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Mucins
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RNA, Messenger
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Rab14 protein, human
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rab GTP-Binding Proteins