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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

PI3K-AKT, JAK2-STAT3 pathways and cell-cell contact regulate maspin subcellular localization

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Autor(es):
Longhi, M. T. [1] ; Silva, L. E. [1] ; Pereira, M. [1] ; Magalhaes, M. [1] ; Reina, J. [1] ; Vitorino, F. N. L. [2] ; Gumbiner, B. M. [3] ; da Cunha, J. P. C. [2] ; Cella, N. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil
[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Ciclo Celular, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil
[3] Univ Washington Sch Med, Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, Dept Pediat & Biochem, 1900 9th Ave Mailstop JMB-5, Seattle, WA 98101 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: CELL COMMUNICATION AND SIGNALING; v. 19, n. 1 AUG 14 2021.
Citações Web of Science: 0
Resumo

Background: Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell-cell contact in this process. Methods: MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell-cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence. Results: We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell-cell adhesion. Conclusions: Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell-cell contact. (AU)

Processo FAPESP: 17/18344-9 - Proteômica quantitativa da cromatina frente ao tratamento com FGF2: análise da regulação transcricional e associação de cdc42
Beneficiário:Francisca Nathália de Luna Vitorino
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 13/00815-4 - O papel de maspina na migração e proliferação celular
Beneficiário:Mariana Tamazato Longhi
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 15/09309-0 - Maspina - funções e vias de sinalização no epitélio mamário murino
Beneficiário:Nathalie Cella
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 15/16384-8 - Regulação da fosforilação de maspina pela via de EGFR
Beneficiário:Mariana Tamazato Longhi
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado