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NOTCH1 regulates migration and invasion of skin cancer cells by E-cadherin repression

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Abstract

NOTCH1 is a regulator that functions not only in tissue development, but also in cancer pathogenesis. We hypothesized that NOTCH1 is involved in skin cancer cell migration and invasion through regulation of E-cadherin and its transcription factor, Snail. Here, using immunofluorescence and western blots, we show that NOTCH1 is upregulated in skin cancer tissue on skin. Inhibition or activation of NOTCH1 altered expression of E-cadherin and Snail in the skin cancer cell line A431. Our results suggest that this effect is through changing DNA methylation levels of the E-cadherin gene promoter. Activation and inhibition of NOTCH1 also altered the behavior of A431 cells in migration and invasion assays in vitro. Our results suggest NOTCH1 is a potential target for discovery of new drug to inhibit skin cancer metastasis.

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Abbreviations

T-ALL:

T-cell acute lymphoblastic leukemia

BCC:

Basal cell carcinoma

EMT:

Epithelial-mesenchymal transition

GSI:

r-secretase inhibitor

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Acknowledgments

This study is sponsored by National Natural Science Foundation of China (No. 81071689, No. 81073135, No. 81001088), Shaanxi Foundation of technology (2010K14-02-07), Research Foundation for the Returned Overseas Scholars in Fourth Military Medical University.

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None.

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Authors and Affiliations

  1. Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, China

    Zhipeng Wang, Meng Wang, Juanjuan Liu, Chen Li, Chunyan Xin, Qibing Mei & Yukun Wang

  2. Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi’an, China

    Linna Liu

  3. Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China

    Min Shen

  4. Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi’an, China

    Jing Li

  5. The Helmholtz Sino-German Research Laboratory for Cancer, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China

    Shaojun Zhu

Authors
  1. Zhipeng Wang
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  2. Linna Liu
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  3. Meng Wang
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  4. Min Shen
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  5. Jing Li
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  6. Juanjuan Liu
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  7. Chen Li
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  8. Chunyan Xin
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  9. Shaojun Zhu
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  10. Qibing Mei
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  11. Yukun Wang
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Corresponding author

Correspondence to Yukun Wang.

Additional information

Zhipeng Wang and Linna Liu contributed equally to this stduy.

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Wang, Z., Liu, L., Wang, M. et al. NOTCH1 regulates migration and invasion of skin cancer cells by E-cadherin repression. Mol Cell Biochem 362, 35–41 (2012). https://doi.org/10.1007/s11010-011-1125-6

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  • DOI: https://doi.org/10.1007/s11010-011-1125-6

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