Mastermind-Like 3 controls proliferation and differentiation in neuroblastoma
AuthorsHeynen, Guus J.J.E.
Basheer, Noorjahan Jagalur
Bajpe, Prashanth Kumar
MetadataShow full item record
AbstractNeuroblastoma cell lines can differentiate upon treatment with retinoic acid (RA), a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen, we identified an unexpected link between RA signaling and mastermindlike 3 (MAML3), a known transcriptional coactivator for NOTCH. Our findings indicate that MAML3 expression leads to the loss of activation of a subset of RA target genes, which hampers RA-induced differentiation and promotes resistance to RA. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the RA receptor, suggesting a direct role for MAML3 in the regulation of these genes. In addition, MAML3 has RA-independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. These results demonstrate an important mechanistic role for MAML3 in proliferation and RA-mediated differentiation.
CitationHeynen G, Nevedomskaya E, Palit S, Basheer N, Lieftink C, Schlicker A, Zwart W, Bernards R, Bajpe P (2016) 'Mastermind-Like 3 controls proliferation and differentiation in neuroblastoma', Molecular Cancer Research, 14 (5), pp.411-422.
JournalMolecular Cancer Research
- Hypoxia but not normoxia promotes Smoothened transcription through upregulation of RBPJ and Mastermind-like 3 in pancreatic cancer.
- Authors: Onishi H, Yamasaki A, Kawamoto M, Imaizumi A, Katano M
- Issue date: 2016 Feb 28
- HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness.
- Authors: Giannini G, Di Marcotullio L, Ristori E, Zani M, Crescenzi M, Scarpa S, Piaggio G, Vacca A, Peverali FA, Diana F, Screpanti I, Frati L, Gulino A
- Issue date: 1999 May 15
- Protein-bound Polysaccharide-K Inhibits Hedgehog Signaling Through Down-regulation of MAML3 and RBPJ Transcription Under Hypoxia, Suppressing the Malignant Phenotype in Pancreatic Cancer.
- Authors: Yamasaki A, Onishi H, Imaizumi A, Kawamoto M, Fujimura A, Oyama Y, Katano M
- Issue date: 2016 Aug
- Promyelocytic leukemia-nuclear body formation is an early event leading to retinoic acid-induced differentiation of neuroblastoma cells.
- Authors: Delaune A, Corbière C, Benjelloun FD, Legrand E, Vannier JP, Ripoll C, Vasse M
- Issue date: 2008 Jan