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Disruption of oncogenic pathways in mucoepidermoid carcinoma: CREB inhibitor 666.15 as a potential therapeutic agent
•The IC50 doses of the CREB inhibitor 666.15 used were low, ranging from 0.042 μM to 0.289 μM.•The drug reduces survival, growth, and invasion, and delays migration of mucoepidermoid carcinoma cells, particularly those harbouring the CRTC1-MAML2 fusion.•CREB inhibition led to the upregulation of E-c...
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Published in: | Oral oncology 2024-12, Vol.159, p.107029, Article 107029 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | •The IC50 doses of the CREB inhibitor 666.15 used were low, ranging from 0.042 μM to 0.289 μM.•The drug reduces survival, growth, and invasion, and delays migration of mucoepidermoid carcinoma cells, particularly those harbouring the CRTC1-MAML2 fusion.•CREB inhibition led to the upregulation of E-cadherin in translocation-positive mucoepidermoid carcinoma cells (UM-HMC-2 and H292).
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. |
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ISSN: | 1368-8375 1879-0593 1879-0593 |
DOI: | 10.1016/j.oraloncology.2024.107029 |