Fibulin-3 Has Anti-Tumorigenic Activities in Cutaneous Squamous Cell Carcinoma.
J Invest Dermatol
; 139(8): 1798-1808.e5, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30738056
ABSTRACT
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Several previous studies have shown that fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of fibulin-3 was downregulated in cSCC tissues compared with normal skin tissues, which was due to fibulin-3 promoter methylation. In vitro, knockdown of fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced migration and invasion abilities. Conversely, overexpression of fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced migration and invasion abilities. These anticarcinogenic effects of fibulin-3 were associated with inhibition of the AKT signaling pathway. Through a mouse xenograft model, we found that fibulin-3 overexpression inhibited the cSCC tumor growth in vivo. Our results suggest that fibulin-3 has anti-tumorigenic activities in cSCC. Downregulation of fibulin-3 is involved in cSCC development and it may serve as a novel therapeutic target of this disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Carcinoma de Células Escamosas
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Regulação Neoplásica da Expressão Gênica
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Proteínas da Matriz Extracelular
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Carcinogênese
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2019
Tipo de documento:
Article