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Deregulation of neuroblastoma-derived myc (N-myc) is a leading cause of malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or on the analysis of the medulloblastoma transcriptome. Here, we have broadly characterized the translatome of medulloblastoma and shown that N-myc unexpectedly drives selective translation of transcripts that promote protein homeostasis. Cancer cells are constantly exposed to proteotoxic stress associated with alterations in protein production or folding. It remains poorly understood how cancers cope with proteotoxic stress to promote their growth. Here, our data revealed that N-myc regulates the expression of specific components (∼5%) of the protein folding machinery at the translational level through the major cap binding protein, eukaryotic initiation factor eIF4E. Reducing eIF4E levels in mouse models of medulloblastoma blocked tumorigenesis. Importantly, targeting Hsp70, a protein folding chaperone translationally regulated by N-myc, suppressed tumor growth in mouse and human medulloblastoma xenograft models. These findings reveal a previously hidden molecular program that promotes medulloblastoma formation and identify new therapies that may have impact in the clinic.
Pubmed ID: 36264168 RIS Download
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View all literature mentionsFluorescence microscope of BZ-X series by KEYENCE CORPORATION of America. Captures high resolution images without the blurring caused by out of focus fluorescent signals. Optical sectioning allows the user to obtain images comparable to those captured on a laser confocal microscope, but in a fraction of the time and without the damaging effects of a laser.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets HSC70 (HSP73)
View all literature mentionsFluorescence microscope of BZ-X series by KEYENCE CORPORATION of America. Captures high resolution images without the blurring caused by out of focus fluorescent signals. Optical sectioning allows the user to obtain images comparable to those captured on a laser confocal microscope, but in a fraction of the time and without the damaging effects of a laser.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets eIF-4E
View all literature mentionsThis polyclonal targets DNAJA2
View all literature mentionsThis polyclonal targets HSP90AB1
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser240/244) (D68F8) XP Rabbit mAb
View all literature mentionsThis monoclonal targets 4E-BP1 (53H11) Rabbit mAb
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis monoclonal targets Akt2
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets n-Myc
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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