Effects of CREB inhibitor in mucoepidermoid carcinoma cell lines

Introduction

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor and about 50% of cases have the CRTC1-MAML2 translocation. The CREB pathway has been associated with the transforming activity of CRTC1-MAML2. The aim of this study was to determine the effects of CREB inhibition on MECs cells behavior in vitro.

Material and Methods

Two translocation-positive (UM-HMC-2 and H292) and one translocation-negative (H253) MEC cell lines were treated with the CREB-inhibitor, 666.15.

Drug IC50 doses were determined for each cell line. Clonogenic and sphere assays were used to assess survival and percentage of cancer stem cells (CSC) and transwell and scratch assays to evaluate the cells invasive and migratory capacity. Immunofluorescence staining was used to analysed the E-cadherin expression upon CREB-inhibitor administration.

Results

The drug significantly reduced the number of surviving colonies and spheres and invasion, and delayed cell invasion in all cell lines, particularly for UM-HMC-2 cells. The expression of E-cadherin was significant higher in treated UM-HMC-2 and H292 cells.

Conclusions

CREB inhibition efficiently impaired MEC key oncogenic behavior associated with metastasis and drug resistance, such as cell invasion and survival, respectively.