CHML promotes liver cancer metastasis by facilitating Rab14 recycle
CHML promotes liver cancer metastasis by facilitating Rab14 recycle
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CHML通过促进Rab14回收促进肝癌转移
DOI：
10.1038/s41467-019-10364-0
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发表时间：
2019-06-07
影响因子：
16.6
通讯作者：
Xie, Dong
中科院分区：
文献类型：
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作者：
Chen, Tian-Wei;Yin, Fen-Fen;Xie, Dong
转移相关复发是肝细胞癌（HCC）预后不良的主要原因，但其机制尚不清楚。在这项研究中，我们报告了无脉络膜样（CHML）的表达在HCC中增加，与HCC患者的生存率低，早期复发和更多的卫星结节相关。CHML以Rab 14依赖的方式促进HCC细胞的迁移、侵袭和转移。机制研究表明，CHML通过护送Rab 14到膜上来促进Rab 14的不断循环。此外，我们确定了几个转移调节因子作为Rab 14阳性囊泡携带的货物，包括Mucin 13和CD 44，这可能有助于CHML的转移促进作用。总之，我们的数据建立CHML作为一个潜在的促进肝癌转移，CHML-Rab 14轴可能是一个有前途的治疗肝癌的目标。
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.