Detalhes bibliográficos
Ano de defesa: |
2010 |
Autor(a) principal: |
Scutti, Jorge Augusto Borin [UNIFESP] |
Orientador(a): |
Não Informado pela instituição |
Banca de defesa: |
Não Informado pela instituição |
Tipo de documento: |
Dissertação
|
Tipo de acesso: |
Acesso aberto |
Idioma: |
por |
Instituição de defesa: |
Universidade Federal de São Paulo (UNIFESP)
|
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: |
|
Link de acesso: |
http://repositorio.unifesp.br/handle/11600/9376
|
Resumo: |
Melanoma is the most aggressive form of skin cancer and its incidence has increased dramatically over the years. The origin of melanoma is neuroectodermal and it results from the proliferation and malignant transformation of melanocytes that originate from the neural crest and migrate to the skin and hair follicles during embryogenesis. The last decade has seen major advances in both cellular and molecular aspects of melanoma biology and therapeutic implications. Knowledge on the regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now recognized that melanoma development is regulated by multiple cascade signaling pathways that affect, motility, growth control, invasion, metabolism, cytokine release and the ability to escape immune response. Here, we demonstrate a novel signaling mechanism whereby silencing of SOCS-1 protein, a negative regulator of Jak/Stat pathway, leads to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS-1 silencing with small hairpin RNA inhibits in vitro growth by cell cycle regulation and S phase arrest, motility inhibition and decreased melanoma cell invasion through Matrigel. Clonogenic assay showed that SOCS-1 acted as a modulator of anoikis resistance. Additionally, downregulation of SOCS-1 expression decreased the expression of epidermal growth factor (EGF), insulin receptor and fibroblast growth factor receptor (FGFR). We further demonstrate by in vivo assay that SOCS-1 silencing inhibits tumor growth and metastatic spread in the lungs. Collectively, these data show that silencing of SOCS-1 protein expression in melanoma cells is a critical event, leading to nontumorigenesis and incapacity to metastasize. |