Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis

被引：90

作者：

Jiang, Keqiu ^{[1
,2
,3
]}

Dong, Chengyong ^{[3
]}

Yin, Zeli ^{[1
,2
,3
]}

Li, Rui ^{[1
,2
,3
]}

Mao, Jiakai ^{[1
,2
,3
]}

Wang, Chengye ^{[1
,2
]}

Zhang, Junlin ^{[1
,2
,3
]}

Gao, Zhenming ^{[3
]}

Liang, Rui ^{[3
]}

Wang, Qi ^{[4
]}

Wang, Liming ^{[1
,2
,3
]}

机构：

[1] Dalian Med Univ, Engn Res Ctr New Mat & Precis Treatment Technol M, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China

[2] Dalian Med Univ, Engn Technol Res Ctr Translat Med, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China

[3] Dalian Med Univ, Affiliated Hosp 2, Div Hepatobiliary & Pancreat Surg, Dept Gen Surg, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China

[4] Dalian Med Univ, Affiliated Hosp 2, Dept Resp Med, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 11期

基金：

中国国家自然科学基金;

关键词：

CELL-LINE; CANCER; INVASION; ESTABLISHMENT; HEPATITIS; P38; PHOSPHORYLATION; MIGRATION; PROTEINS; VIRUS;

D O I：

10.1038/s41419-020-03179-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 alpha 6 beta 4 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.

引用

页数：20

共 78 条

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