Identification of CRTC1-MAML2/MAML2-regulated transcriptional program in H3118 cells

Mucoepidermoid carcinomas (MEC) is the most common salivary gland malignancy. To date, advanced and nonresectable MEC have poor prognosis and no effective treatment. The CRTC1-MAML2 fusion oncogene, which is associated with more than 50% of MEC, consists of the N-terminal CREB-binding domain of the CREB transcriptional co-activator CRTC1 and the C-terminal transcriptional activation domain of the Notch transcriptional co-activator MAML2. CRTC1-MAML2 fusion was found to interact with CREB and constitutively activate their transcriptional targets. To investigate the genes and pathways regulated by CRTC1-MAML2 fusion oncogene, gene expression profiling analysis were performed in human fusion-positive MEC cells before and after knockdown of both CRTC1-MAML2 and MAML2 as well as in human fusion-negative salivary gland cancer cells before and after MAML2 knockdown only. This study revealed specific transcriptional program induced by the CRTC1-MAML2 fusion oncogene, which potentially mediates CRC1-MAML2 functions in MEC initiation and maintenance. The information will be useful for developing new approaches to block CRTC1-MAML2 fusion-expressing MEC.

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Chen Z, Chen J, Gu Y, Hu C, Li JL, Lin S, Shen H, Cao C, Gao R, Li J, Ha PK, Kaye FJ, Griffin JD, Wu L