Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis.
Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis.
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DOI：
10.1038/s41419-020-03179-1
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发表时间：
2020-11-12
影响因子：
9
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Jiang K;Dong C;Yin Z;Li R;Mao J;Wang C;Zhang J;Gao Z;Liang R;Wang Q;Wang L
已发现α-烯醇化酶（ENO 1）在包括肝细胞癌（HCC）在内的几种人类恶性肿瘤中失调。尽管ENO 1作为肝癌细胞中糖酵解酶的作用已得到充分表征，但人们对ENO 1（尤其是外泌体来源的ENO 1）在调节肝癌进展中的其他作用知之甚少。在这里，我们证明了ENO 1在HCC细胞或组织中经常上调，在高转移性HCC细胞或转移性组织以及来源于高转移性来源的外来体中表达甚至更高。此外，ENO 1表达与HCC患者的肿瘤淋巴结转移（TNM）分期、分化程度和不良预后相关。令人惊讶的是，ENO 1可以通过外泌体介导的串扰在HCC细胞之间转移，表现出类似于HCC细胞中ENO 1过表达的效果，其通过上调整合素α6β4表达和激活FAK/Src-p38 MAPK通路促进具有低ENO 1表达的HCC细胞的生长和转移。总之，我们的数据表明，外泌体来源的ENO 1是必不可少的，以促进肝癌的生长，转移，并进一步恶化患者。这项研究的结果暗示了一种新的生物标志物，用于临床评估HCC进展，特别是预测HCC转移风险。
Alpha-enolase (ENO1) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). Although the role of ENO1 as a glycolytic enzyme in HCC cells has been well characterized, little is known about the other roles of ENO1, especially exosome-derived ENO1, in regulating HCC progression. Here, we demonstrated that ENO1 is frequently upregulated in HCC cells or tissues, with even higher expression in highly metastatic HCC cells or metastatic tissues as well as in exosomes derived from highly metastatic sources. Moreover, ENO1 expression is associated with the tumor-node-metastasis (TNM) stage, differentiation grade and poor prognosis in HCC patients. Surprisingly, ENO1 can be transferred between HCC cells via exosome-mediated crosstalk, exhibiting an effect similar to that of ENO1 overexpression in HCC cells, which promoted the growth and metastasis of HCC cells with low ENO1 expression by upregulating integrin α6β4 expression and activating the FAK/Src-p38MAPK pathway. In summary, our data suggest that exosome-derived ENO1 is essential to promoting HCC growth, metastasis, and further patient deterioration. The findings from this study implicate a novel biomarker for the clinical evaluation of HCC progression, especially the prediction of HCC metastatic risk.
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影响因子：
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作者：
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影响因子：
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通讯作者：
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