Mutant IDH1 is required for IDH1 mutated tumor cell growth.
Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we report that selective suppression of endogenous mutant IDH1 expression in HT1080, a fibrosarcoma cell line with a native IDH1(R132C) heterozygous mutation, significantly inhibits cell proliferation and decreases clonogenic potential. Our findings offer insights into changes that may contribute to the inhibition of cell proliferation and offer a strong preclinical rationale for utilizing mutant IDH1 as a valid therapeutic target.
Duke Scholars
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- RNA, Small Interfering
- RNA Interference
- Mutation
- Isocitrate Dehydrogenase
- Humans
- Fibrosarcoma
- Cell Proliferation
- Cell Line, Tumor
- 3211 Oncology and carcinogenesis
- 1112 Oncology and Carcinogenesis
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- RNA, Small Interfering
- RNA Interference
- Mutation
- Isocitrate Dehydrogenase
- Humans
- Fibrosarcoma
- Cell Proliferation
- Cell Line, Tumor
- 3211 Oncology and carcinogenesis
- 1112 Oncology and Carcinogenesis