Journal article
A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells
Nature communications, v 10(1), pp 5444-15
29 Nov 2019
PMID: 31784510
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport. Milciclib blocks glucose consumption by targeting cyclin-dependent kinase 7 (CDK7) similar to other CDK7 inhibitors including THZ1 and LDC4297. Enhanced PIK3CA signaling leads to CDK7 phosphorylation, which promotes RNA Polymerase II phosphorylation and transcription. Milciclib, THZ1, and LDC4297 lead to a reduction in RNA Polymerase II phosphorylation on the SLC2A1 promoter. These data indicate that our high-throughput assay can identify compounds that regulate glucose consumption and that CDK7 is a key regulator of glucose consumption in cells with an activated PI3K pathway.
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Details
- Title
- A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells
- Creators
- Chiara Ghezzi - University of California, Los AngelesAlicia Wong - University of California, Los AngelesBao Ying Chen - University of California, Los AngelesBernard Ribalet - University of California, Los AngelesRobert Damoiseaux - University of California, Los AngelesPeter M Clark - Crump Institute for Molecular Imaging, University of California, Los Angeles, USA
- Publication Details
- Nature communications, v 10(1), pp 5444-15
- Publisher
- Springer Nature
- Grant note
- P30 CA016042 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000500471200001
- Scopus ID
- 2-s2.0-85075793893
- Other Identifier
- 991019356496704721
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- Web of Science research areas
- Biochemistry & Molecular Biology