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ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway

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Tumor Biology

Abstract

ARMC8 proteins are novel armadillo repeat containing proteins, which are well conserved in eukaryotes and are involved in a variety of processes such as cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. Armadillo repeat proteins include well-known proteins such as β-catenin and p120ctn. Our current knowledge of ARMC8, especially its role in cancer, is limited. In this study, we quantified ARMC8 expression in 112 non-small cell lung cancer (NSCLC) tissues and adjacent non-cancerous tissues, and seven lung cancer cell lines using immunohistochemistry staining and Western blotting. ARMC8 level was significantly higher in NSCLC tissues than in the adjacent normal tissues (67.9 % versus 5.4 %, p < 0.05) and was significantly associated with TNM stage (p = 0.022), lymph node metastasis (p = 0.001), and poor prognosis (p < 0.001) in NSCLC patients. Cox regression analysis demonstrated that ARMC8 was an independent prognostic factor for NSCLC. Consistent with this, ARMC8α downregulation by siRNA knockdown inhibited growth, colony formation, and invasion in A549 lung cancer cells, while ARMC8α overexpression promoted growth, colony formation, and invasion in H1299 lung cancer cells. In addition, ARMC8α knockdown downregulated canonical Wnt-signaling pathway activity and cyclin D1 and matrix metalloproteinase (MMP)-7 expression. Consistent with this, ARMC8α overexpression upregulated canonical Wnt-signaling pathway activity and cyclin D1 and MMP-7 expression. These results indicate that ARMC8α upregulates cyclin D1 and MMP7 expression by activating the canonical Wnt-signaling pathway and thereby promoting lung cancer cell proliferation and invasion. Therefore, ARMC8 might serve as a novel therapeutic target in NSCLC.

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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. 81272606 to Enhua Wang, No. 81301837 to Juanhan Yu and No.81101779 to Di 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

    Chengyao Xie, Guiyang Jiang, Chuifeng Fan, Xiupeng Zhang, Yong Zhang, Yuan Miao, Xuyong Lin, Junhua Wu, Liang Wang, Yang Liu, Juanhan Yu, Lianhe Yang, Di Zhang & Enhua Wang

  2. Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, China

    Ke Xu

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  1. Chengyao Xie
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  2. Guiyang Jiang
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  3. Chuifeng Fan
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  4. Xiupeng Zhang
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  5. Yong Zhang
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  6. Yuan Miao
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  7. Xuyong Lin
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  8. Junhua Wu
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  9. Liang Wang
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  10. Yang Liu
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  11. Juanhan Yu
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  12. Lianhe Yang
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  13. Di Zhang
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  14. Ke Xu
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  15. Enhua Wang
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Correspondence to Enhua Wang.

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Xie, C., Jiang, G., Fan, C. et al. ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway. Tumor Biol. 35, 8903–8911 (2014). https://doi.org/10.1007/s13277-014-2162-z

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  • DOI: https://doi.org/10.1007/s13277-014-2162-z

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