NOTCH1 regulates migration and invasion of skin cancer cells by E-cadherin repression.
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.
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
Z
Wang
Linna
L
Liu
Meng
M
Wang
Min
M
Shen
Jing
J
Li
Juanjuan
J
Liu
Chen
C
Li
Chunyan
C
Xin
Shaojun
S
Zhu
Qibing
Q
Mei
Yukun
Y
Wang
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D015820:Cadherins; C497761:NOTCH1 protein, human; D009842:Oligopeptides; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C523462:benzyloxycarbonyl-leucyl-leucyl-norleucinal