Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-10523-3
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Funding
- US National Institutes of Health National Institute of Diabetes, Digestive and Kidney Diseases Career Development Award [NIDDK NIH R01-DK101989-01A1, NCI 1R01CA193842-01]
- Louis V. Gerstner Young Investigator Award
- American Society of Hematology Junior Scholar Award
- Kimmel Scholar Award
- V-Scholar Award
- Geoffrey Beene Award
- Alex's Lemonade Stand A Award
- Starr Foundation
- Commonwealth Foundation for Cancer Research
- Center for Experimental Therapeutics at Memorial Sloan Kettering Cancer Center
- NIH/NCI Cancer Support Core Grant [P30 CA08748]
- Sloan Kettering Institute
- NIH [P30 CA008748, R01 GM121505, S10OD016432]
- Merck KGaA
- Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the National Institutes of Health [T32GM007739]
- National Cancer Institute [P30-CA008748]
- National Institutes of Health [P41GM103403, HEI-S10RR029205]
- Department of Energy [DE-AC02-06CH11357]
- NYSTAR
- ORIP/NIH facility improvement grant [CO6RR015495]
- [T32 CA062948-Gudas]
Ask authors/readers for more resources
The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.
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