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Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition

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Abstract

Discoidin domain receptors (DDRs) are a novel class of receptor tyrosine kinases that respond to several collagens and facilitate cell adhesion. DDR1 is highly expressed in a variety of human cancers, and it is clear that DDR1 is primarily expressed in epithelial cells including lung, colon and brain. Moreover, DDR1 expression can be stimulated by collagen types I, II, III, IV, V, VIII and XI, and aberrant signaling induced by DDR1 dysregulated expression is involved in various steps of tumorigenesis. However, the molecular mechanism underlying the role of DDR1 in cancer development is not well documented. In this study, we found that the expression of DDR1 is upregulated in non-small cell lung cancer (NSCLC) tissues and cells when compared with counterpart normal tissues and cells. Furthermore, collagen I could induce DDR1 expression, and activated DDR1 promoted NSCLC cell migration and invasion, while knockdown of DDR1 by transfection with siRNA resulted in a significant decrease in cell migrativeness and invasiveness. Enhanced DDR1 expression mediated by collagen I could activate MMP-2, N-cadherin and vimentin expression, but reduce E-cadherin expression; however, inhibition of DDR1 expression could suppress MMP-2, N-cadherin and vimentin expression and induce E-cadherin activation. In conclusion, our findings indicated that upregulation of DDR1 induced by collagen I may contribute to the development and progression of NSCLC and this effect may be associated with increased invasiveness, at least in part, via promoting epithelial-to-mesenchymal transition.

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Acknowledgments

This research was supported by the Natural Science Fund of Jiangsu Province (BK2011658) to Song Yong.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China

    Liyun Miao, Yongsheng Wang, Yan Li, Jingjing Ding, Jinghong Dai, Hourong Cai & Deping Zhang

  2. Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

    Suhua Zhu & Yong Song

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  1. Liyun Miao
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Correspondence to Yong Song.

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Miao, L., Zhu, S., Wang, Y. et al. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition. Med Oncol 30, 626 (2013). https://doi.org/10.1007/s12032-013-0626-4

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  • DOI: https://doi.org/10.1007/s12032-013-0626-4

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