CHML promotes liver cancer metastasis by facilitating Rab14 recycle.
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.
Duke Scholars
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- rab GTP-Binding Proteins
- Tumor Burden
- RNA, Messenger
- Neoplasms, Multiple Primary
- Neoplasm Transplantation
- Neoplasm Recurrence, Local
- Neoplasm Invasiveness
- Mucins
- Mice, Nude
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- rab GTP-Binding Proteins
- Tumor Burden
- RNA, Messenger
- Neoplasms, Multiple Primary
- Neoplasm Transplantation
- Neoplasm Recurrence, Local
- Neoplasm Invasiveness
- Mucins
- Mice, Nude
- Mice