CHML promotes liver cancer metastasis by facilitating Rab14 recycle.

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.

• Authors: 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, Dong Xie
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 2510 (06 07 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31175290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• CD44 protein, human
• CHML protein, human
• Hyaluronan Receptors
• MUC13 protein, human
• Mucins
• RNA, Messenger
• Rab14 protein, human
• rab GTP-Binding Proteins

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Animals
• Carcinoma, Hepatocellular (genetics, metabolism, secondary)
• HEK293 Cells
• Humans
• Hyaluronan Receptors (metabolism)
• Liver Neoplasms (genetics, metabolism, pathology)
• Lung Neoplasms (metabolism, secondary)
• Mice
• Mice, Nude
• Mucins (metabolism)
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local (genetics, metabolism)
• Neoplasm Transplantation
• Neoplasms, Multiple Primary (metabolism, pathology)
• RNA, Messenger (metabolism)
• Tumor Burden
• rab GTP-Binding Proteins (metabolism)