CHML promotes liver cancer metastasis by facilitating Rab14 recycle.

Nature communications 2019 Jun 07

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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.

Citation

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. CHML promotes liver cancer metastasis by facilitating Rab14 recycle. Nature communications. 2019 Jun 07;10(1):2510