CHML通过Rab14循环促进肝癌转移的分子机制

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. Metastasis-associated recurrence is a major cause of poor prognosis in hepatocellular carcinoma. Here, the authors show that expression of choroideremia-like (CHML) is elevated and associates with poor prognosis in hepatocellular carcinoma, and mechanistically CHML promotes metastasis in a Rab14-dependent manner.