Mutant IDH1 Expression Drives TERT Promoter Reactivation as Part of the Cellular Transformation Process
نویسندگان
چکیده
منابع مشابه
NFκB drives TERT promoter reactivation in cancer
Transformed cells from 80 to 85% of human cancers display measureable levels of active TERT, the reverse transcriptase subunit of telomerase which is essential for growth and survival of these cells. It is well known that the TERT promoter is transcriptionally silenced in development soon after stem cells loose stemness and differentitae. Although interesting from the point of view of regenerat...
متن کاملMutant IDH1-driven cellular transformation increases RAD51-mediated homologous recombination and temozolomide resistance.
Isocitrate dehydrogenase 1 (IDH1) mutations occur in most lower grade glioma and not only drive gliomagenesis but are also associated with longer patient survival and improved response to temozolomide. To investigate the possible causative relationship between these events, we introduced wild-type (WT) or mutant IDH1 into immortalized, untransformed human astrocytes, then monitored transformati...
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Cancer-specific TERT promoter mutations (-146C>T and -124C>T) have been linked to reactivation of the epigenetically silenced telomerase reverse transcriptase gene (TERT). Understanding how these single-nucleotide alterations drive TERT reactivation is a fundamental unanswered question and is key for making successful therapeutics. We show that unlike wild-type promoters, recruitment of the tra...
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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 repor...
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Cdc42Hs is a small GTPase of the Rho-subfamily, which regulates signaling pathways that influence cell morphology and polarity, cell-cycle progression and transcription. An essential role for Cdc42Hs in cell growth regulation has been suggested by the finding that the Dbl oncoprotein is an upstream activator-a guanine nucleotide exchange factor (GEF)-for Cdc42Hs, and that activated mutants of t...
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ژورنال
عنوان ژورنال: Cancer Research
سال: 2016
ISSN: 0008-5472,1538-7445
DOI: 10.1158/0008-5472.can-16-0696