A recent study led by Dr. XIE Dong’s group from Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences revealed the role and mechanism of choroideremia-like (CHML) in liver cancer metastasis, providing therapeutic targets for treatment of liver cancer. The study was published online in Nature Communications on June 7.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, ranking as the second leading cause of cancer-related death. Metastasis-associated recurrence is the major cause of poor prognosis in HCC, however, the underlying mechanisms remain largely elusive. 

In this study, researchers reported that the expression of CHML was increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients.

Mechanism study revealed that CHML facilitated constant recycling of Rab14 by escorting Rab14 to the membrane.

Furthermore, they identified several metastasis regulators as cargoes carried by Rab14-positive vesicles, including Mucin13 and CD44, which may contribute to metastasis-promoting effects of CHML.  

This study illustrated the metastasis-enhancing function of CHML in HCC, which was mediated by vesicle transport of Rab14. Since CHML was overexpressed in more than 80% HCC tissues examined, activation of CHML-Rab14 axis might be a general oncogenic event in HCC, which provides a potential therapeutic target for HCC metastasis. 

CHML interacts with Rab14, and escorts Rab14 to the membrane, which regulates the membrane localization of metastasis-related molecules carried by Rab14-positive vesicles. (Image by Dr. XIE Dong's Group)