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Disruption of oncogenic pathways in mucoepidermoid carcinoma: CREB inhibitor 666.15 as a potential therapeutic agent

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Autor(es):
Perez-de-Oliveira, Maria Eduarda ; Wagner, Vivian Petersen ; Bingle, Colin D. ; Vargas, Pablo Agustin ; Bingle, Lynne
Número total de Autores: 5
Tipo de documento: Artigo Científico
Fonte: Oral Oncology; v. 159, p. 8-pg., 2024-09-26.
Resumo

Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour with around 50 % of cases carrying the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of this translocation. The aim of this study was to determine the effects of CREB inhibition on MEC cell behaviour in vitro. . Material and Methods: Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with 666.15, a CREB inhibitor. Drug IC50 doses were determined for each cell line. Clonogenic and spheroid assays were used to assess survival, including percentage of cancer stem cells, and transwell and scratch assays evaluated invasive and migratory capacities, respectively. Immunofluorescence staining was used to determine E-cadherin expression. Results: CREB inhibition significantly reduced the number of surviving colonies and spheroids and delayed cell invasion in all cell lines, but this was more significant in the fusion positive, UM-HMC-2 cells. The expression of E-cadherin was significantly higher in treated UM-HMC-2 and H292 cells. Conclusion: CREB inhibition with 666.15 impaired key MEC oncogenic behaviours associated with metastasis and drug resistance, including cell invasion and survival. (AU)

Processo FAPESP: 19/26676-7 - Desvendando o papel da translocação CRTC1-MAML2 no Carcinoma Mucoepidermoide de glândula salivar: um estudo clínico-patológico, molecular e proteômico
Beneficiário:Maria Eduarda Pérez de Oliveira
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 21/10810-6 - Biotinilação dependente de proximidade para a identificação de proteínas que interagem com células de glândula salivar transfectadas com a translocação CRTC1-MAML2
Beneficiário:Maria Eduarda Pérez de Oliveira
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado