ApoC1 promotes the metastasis of clear cell renal cell carcinoma via activation of STAT3
ApoC1 promotes the metastasis of clear cell renal cell carcinoma via activation of STAT3
复制标题
ApoC1通过激活STAT3促进透明细胞肾细胞癌的转移
DOI：
10.1038/s41388-020-01428-3
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发表时间：
2020-08-21
期刊：
影响因子：
8
通讯作者：
Lin, Neng-ming
中科院分区：
文献类型：
--
作者：
Li, Yang-ling;Wu, Lin-wen;Lin, Neng-ming
透明细胞肾细胞癌（CCRCC）是最常见的肾癌，经常在晚期诊断出。即使经过适当的治疗，也很容易发展不可预测的转移。抗血管生成疗法是转移性CCRC的最有效的医疗。因此，对抑制血管生成和转移的新方法的探索可能会导致CCRC的更好的治疗选择。在所有类型的癌症中，肾脏癌样品表现出对Comcomine数据库中APOC1的最大上调。伴随CCRCC进展的APOC1的表达增加。高水平的APOC1与CCRCC患者的生存时间密切相关。此外，与低侵入性CCRCC细胞相比，APOC1在高度侵入性的CCRCC细胞中过表达。此外，APOC1通过EMT途径促进了CCRCC细胞的转移，而APOC1的耗竭减轻了这些作用。 APOC1作为一种新型的促量因子促进了STAT3的激活并增强了CCRCC细胞的转移。同时，外泌体中的APOC1从CCRCC细胞转移到血管内皮细胞，并通过激活STAT3促进CCRCC细胞的转移。最后，DPP-4抑制抑制了由APOC1驱动的CCRCC细胞的转移电位。我们的研究不仅确定了CCRCC转移中新型的APOC1-STAT3途径，而且还为未来预测和治疗转移性CCRCC的新型策略提供了方向。
Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer and frequently diagnosed at an advanced stage. It is prone to develop unpredictable metastases even with proper treatment. Antiangiogenic therapy is the most effective medical treatment for metastatic ccRCC. Thus, exploration of novel approaches to inhibit angiogenesis and metastasis may potentially lead to a better therapeutic option for ccRCC. Among all the types of cancer, renal cancer samples exhibited the maximum upregulation of ApoC1 as referred to in the Oncomine database. The expression of ApoC1 was increased accompanied by ccRCC progression. A high level of ApoC1 was closely related to poor survival time in ccRCC patients. Furthermore, ApoC1 was over-expressed in the highly invasive ccRCC cells as compared to that in the low-invasive ccRCC cells. Besides, ApoC1 promoted metastasis of ccRCC cells via EMT pathway, whereas depletion of ApoC1 alleviated these effects. ApoC1 as a novel pro-metastatic factor facilitates the activation of STAT3 and enhances the metastasis of ccRCC cells. Meanwhile, ApoC1 in the exosomes were transferred from the ccRCC cells to the vascular endothelial cells and promoted metastasis of the ccRCC cells via activating STAT3. Finally, the metastatic potential of the ccRCC cells driven by ApoC1 was suppressed by DPP-4 inhibition. Our study not only identifies a novel ApoC1-STAT3 pathway in ccRCC metastasis but also provides direction for the exploration of novel strategies to predict and treat metastatic ccRCC in the future.