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MXR7 facilitates liver cancer metastasis via epithelial-mesenchymal transition

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81622039, 81572895, 81372356, 81221061), Shanghai Subject Chief Scientist(14XD1400100).

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Authors and Affiliations

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

    Guishuai Lv, Yexiong Tan, Hongwei Lv, Tian Fang, Changzheng Wang, Ting Li, Yanting Yu, Congli Hu, Wen Wen, Hongyang Wang & Wen Yang

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

    Guishuai Lv, Yexiong Tan, Yanting Yu, Congli Hu, Wen Wen, Hongyang Wang & Wen Yang

  3. State Key Laboratory of Oncogenes and related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China

    Hongyang Wang

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  1. Guishuai Lv
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  2. Yexiong Tan
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  3. Hongwei Lv
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  4. Tian Fang
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Correspondence to Hongyang Wang or Wen Yang.

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Lv, G., Tan, Y., Lv, H. et al. MXR7 facilitates liver cancer metastasis via epithelial-mesenchymal transition. Sci. China Life Sci. 60, 1203–1213 (2017). https://doi.org/10.1007/s11427-016-9042-y

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