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Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyond photoreceptor lineage genes, we identify BCL-XL as a key transcriptional target of NRL and provide evidence substantiating anti-BCL therapy as a rational treatment opportunity for select MB patients. Our results highlight the utility of studying aberrant differentiation programs in cancer and their potential as selective therapeutic vulnerabilities.
Pubmed ID: 29533784 RIS Download
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View all literature mentionsThis polyclonal targets Human NRL
View all literature mentionsCell line Daoy is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Daoy is a Cancer cell line with a species of origin Homo sapiens (Human)
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