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Published on: February 28, 2017
NOTCH1 regulates migration and invasion of skin cancer cells by E-cadherin repression
Zhipeng Wang1, Linna Liu, Meng Wang
1Key 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.
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.
Insights
NOTCH1 signaling impacts skin cancer progression by regulating E-cadherin and Snail. Targeting NOTCH1 may offer new strategies to inhibit skin cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- NOTCH1 is a key regulator in tissue development and cancer.
- Skin cancer cell migration and invasion are critical for metastasis.
Purpose of the Study:
- To investigate the role of NOTCH1 in skin cancer cell migration and invasion.
- To determine if NOTCH1 regulates E-cadherin and Snail expression in skin cancer.
Main Methods:
- Immunofluorescence and western blot analysis to assess protein expression.
- In vitro migration and invasion assays.
- DNA methylation analysis of the E-cadherin gene promoter.
Main Results:
- NOTCH1 was upregulated in skin cancer tissue.
- NOTCH1 modulation affected E-cadherin and Snail expression in A431 cells.
- Changes in E-cadherin promoter DNA methylation were observed.
- NOTCH1 activity influenced skin cancer cell migration and invasion in vitro.
Conclusions:
- NOTCH1 plays a significant role in skin cancer cell migration and invasion.
- NOTCH1 may exert its effects through epigenetic modifications of the E-cadherin promoter.
- NOTCH1 represents a potential therapeutic target for inhibiting skin cancer metastasis.
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