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ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells

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Tumor Biology

Abstract

Recent studies have implicated ARMc8 in promoting tumor formation in non-small cell lung cancer and breast cancer; however, so far, no studies have revealed the expression pattern or cellular function of ARMc8 in colon cancer. In this study, we used immunohistochemical staining to measure ARMc8 expression in 206 cases of colon cancer and matched adjacent normal colon tissue. Clinically important behaviors of cells, including invasiveness and migration, were evaluated after upregulation of ARMc8 expression in HT29 cells through gene transfection or downregulation of expression in LoVo cells using RNAi. We found that ARMc8 was primarily located in the membrane and cytoplasm of tumor cells, and its expression level was significantly higher in colon cancer in comparison to that in the adjacent normal colon tissues (p < 0.001). ARMc8 expression was closely related to TNM stage (p = 0.006), lymph node metastasis (p = 0.001), and poor prognosis (p = 0.002) of colon cancer. The invasiveness and migration capacity of HT29 cells transfected with ARMc8 were significantly greater than those of control cells (p < 0.001), while ARMc8 siRNA treatment significantly reduced cell invasion and migration in LoVo cells (p < 0.001). Furthermore, we demonstrated that ARMc8 could upregulate the expression of MMP7 and snail and downregulate the expression of p120ctn and α-catenin. Therefore, ARMc8 probably enhanced invasiveness and metastatic capacity by affecting these tumor-associated factors, thereby playing a role in enhancing the tumorigenicity of colon cancer cells. ARMc8 is likely to become a potential therapeutic target for colon cancer.

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Acknowledgments

The authors thank Prof. Ishigatsubo Y, Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, for kindly providing ARMc8 pcDNA. This study was supported by the National Natural Science Foundation of China (No. 81402369 to Guiyang Jiang, No. 81272606 to EnhuaWang, No. 81472599 to Chuifeng Fan, No. 81302192 to Liang Wang) and the Natural Science Foundation of Liaoning Province (No. 2013021049 to Yong Zhang).

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Authors and Affiliations

  1. Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China

    Guiyang Jiang, Yong Zhang, Xiupeng Zhang, Chuifeng Fan, Liang Wang, Hongtao Xu, Juanhan Yu & Enhua Wang

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  1. Guiyang Jiang
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  2. Yong Zhang
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  3. Xiupeng Zhang
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  4. Chuifeng Fan
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  5. Liang Wang
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  7. Juanhan Yu
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  8. Enhua Wang
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Correspondence to Enhua Wang.

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Jiang, G., Zhang, Y., Zhang, X. et al. ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells. Tumor Biol. 36, 9005–9013 (2015). https://doi.org/10.1007/s13277-015-3664-z

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  • DOI: https://doi.org/10.1007/s13277-015-3664-z

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