Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] M-phase cell cycle genes in human breast cancer cells
Open accessAbstract
Prompted by the ever-growing scientific rationale for examining the antidiabetic drug metformin as a potential antitumor agent in breast cancer disease, we recently tested the hypothesis that the assessment of metformin-induced global changes in gene expression-as identified using 44 K (double density) Agilent's whole human genome arrays-could reveal gene-expression signatures that would allow proper selection of breast cancer patients who should be considered for metformin-based clinical trials. Using Database for Annotation, Visualization and Integrated Discovery bioinformatics (DAVID) resources we herein reveal that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only downregulates genes coding for ribosomal proteins (i.e., protein and macromolecule biosynthesis) but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases. This is, to our knowledge, the first genome-scale evidence of a mitotic core component in the transcriptional response of human breast cancer cells to metformin. These findings further support a tight relationship between the activation status of AMPK and the chromosomal and cytoskeletal checkpoints of cell mitosis at the transcriptional level.
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Metformin may selectively kill cancer stem cells and enhance effectiveness of breast cancer treatment regimens.
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From Diabetes and Cancer (2010) · cites this paper as [87]
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A role for AMPK in the regulation of mitosis and cytokinesis
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- Authors
- Oliveras-Ferraros, C., Vazquez-Martin, A., & Menendez, J. A.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2009-05-15
- Volume
- 8
- Issue
- 10
- Pages
- 1633-1636
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2074782537
- Cited by
- 52
- References
- 0
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 8 · 2012: 3
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell Cycle (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- metformin, AMPK, breast cancer, mitosis, kinesin, tubulin, histones, Aurora kinases, Polo-like kinase, ribosomal proteins, gene expression profiling, cell cycle checkpoints, cytoskeleton
- MeSH terms
- Breast Neoplasms, Cell Division, Histones, Humans, Metformin, Tubulin, Signal Transduction, Genome, Human, Gene Expression Regulation, Neoplastic, Kinesins, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cell Line, Tumor, AMP-Activated Protein Kinases, Aurora Kinases
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