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Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma

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Abstract

High levels of S100A6 have been associated with poor outcome in some types of human cancers, but the role of S100A6 in the molecular pathogenesis of these cancers is largely unknown. This study was performed to explore the expression and functional roles of S100A6 in hepatocellular carcinoma (HCC). The expression level of S100A6 in HCC tumor and corresponding peritumoral tissues were determined by immunohistochemistry analysis. The potential functions of S100A6 in tumorigenesis and metastasis were analyzed by cell proliferation, migration, and invasion assays in human liver cancer cells. Moreover, through expression and purification of S100A6 recombinant protein tagged with cell-penetrating peptide, we analyzed its complex extracellular/intracellular effects in a S100A6-silenced cellular model. As a result, the expression of S100A6 was up-regulated in human HCC compared with adjacent peritumoral tissues. S100A6 silencing inhibited the growth and motility of HCC cells, while intracellular re-expression of S100A6 could rescue the proliferation and migration defects. Intracellular over-expression of S100A6 resulted in down-regulation of E-cadherin expression and promoted nuclear accumulation of β-catenin. Moreover, we found that the enhanced cell proliferation and motility after S100A6 stimulation were dependent on the activation of PI3K/AKT pathway. These results suggest that S100A6 may be involved in promotion and progression of human liver cancer.

Key Messages

  • S100A6 is overexpressed in human hepatocellular carcinoma clinical specimens.

  • S100A6 promotes proliferation and migration of human hepatoma cells.

  • Overexpression of S100A6 results in alteration of E-cadherin and β-catenin.

  • The multi-effects of S100A6 may be mediated in part by PI3K/AKT pathway activation.

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Abbreviations

HCC:

Hepatocellular carcinoma

CPP:

Cell-penetrating peptide

CCA:

Cholangiocarcinoma

RAGE:

Receptor for activated glycation end products

MMPs:

Matrix metalloproteinases

EMT:

Epithelial-to-mesenchymal transition

Dox:

Doxycycline

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Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (30900768), and by the National 973 Basic Research Program of China (2010CB529900 and 2011CB910703).

Competing interests

The authors declare no conflict of interests related to this study.

Author information

Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China

    Ziqiang Li, Mei Tang, Bo Ling, Shiying Liu, Yu Zheng, Chunlai Nie, Zhu Yuan, Gang Guo, Aiping Tong & Yuquan Wei

  2. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Liangxue Zhou

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  1. Ziqiang Li
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  2. Mei Tang
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Correspondence to Aiping Tong.

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Ziqiang Li and Mei Tang contributed equally to this work.

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Li, Z., Tang, M., Ling, B. et al. Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma. J Mol Med 92, 291–303 (2014). https://doi.org/10.1007/s00109-013-1104-3

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  • DOI: https://doi.org/10.1007/s00109-013-1104-3

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