MXR7 通过上皮-间质转化促进肝癌转移。

MXR7 facilitates liver cancer metastasis via epithelial-mesenchymal transition.

机构信息

International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, China.

National Center for Liver Cancer, Shanghai, 201805, China.

出版信息

Sci China Life Sci. 2017 Nov;60(11):1203-1213. doi: 10.1007/s11427-016-9042-y. Epub 2017 Aug 11.

DOI:10.1007/s11427-016-9042-y

PMID:28812296

Abstract

MXR7 is a cell-surface protein and highly expressed in hepatocellular carcinoma (HCC). The aim of this study is to determine the expression profile of MXR7 in HCC and investigate the influence of MXR7 on invasion and metastasis of HCC cells. For this purpose, immunohistochemical assay was used to identify the differential expression of MXR7 in 94 HCC specimens. Expression of MXR7 in 4 pairs of HCC and portal vein tumor thrombus (PVTT) was also tested. The motility of HCC cells were characterized by transwell migration and matrigel invasion assays. In vivo metastasis potential was determined via tail vein injection assay. Moreover, compared with noninvasive HCC tumors or human HCC cell lines with low metastatic potential, invasive HCC samples and HCC cell lines with high metastatic potential exhibited higher MXR7 expression. Furthermore, forced expression of MXR7 in SMMC-7721 promoted cell proliferation, migration and invasion in vitro and accelerated tumor growth and metastasis in vivo. Conversely, knockdown of MXR7 expression in HuH7 cells inhibited proliferation and motility of cells. Mechanically, overexpression of MXR7 promoted epithelial-mesenchymal transition (EMT) progress, and MXR7 depletion repressed the EMT phenotype. In conclusion, MXR7 is a mediator of EMT and metastasis in HCC and may serve as a novel therapeutic target.

摘要

MXR7 是一种细胞表面蛋白，在肝细胞癌（HCC）中高度表达。本研究旨在确定 MXR7 在 HCC 中的表达谱，并研究 MXR7 对 HCC 细胞侵袭和转移的影响。为此，采用免疫组织化学法检测 94 例 HCC 标本中 MXR7 的差异表达。还检测了 4 对 HCC 和门静脉癌栓（PVTT）中 MXR7 的表达。通过 Transwell 迁移和 Matrigel 侵袭实验来表征 HCC 细胞的迁移能力。通过尾静脉注射实验来确定体内转移潜能。此外，与无侵袭性 HCC 肿瘤或低转移潜能的人 HCC 细胞系相比，侵袭性 HCC 样本和高转移潜能的 HCC 细胞系表现出更高的 MXR7 表达。此外，在 SMMC-7721 中强制表达 MXR7 可促进体外细胞增殖、迁移和侵袭，并加速体内肿瘤生长和转移。相反，HuH7 细胞中 MXR7 表达的下调抑制了细胞的增殖和迁移能力。在机制上，MXR7 的过表达促进了上皮间质转化（EMT）的进展，而 MXR7 的耗竭则抑制了 EMT 表型。总之，MXR7 是 HCC 中 EMT 和转移的介质，可能成为一种新的治疗靶点。