Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
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Thiru-2014-Kinetochore genes are.pdf
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Author(s)
Thiru, Prathapan
Kern, David Matthew
McKinley, Kara Lavidge
Monda, Julie Kathryn
Rago, Florencia
Su, Kuan-Chung
Tsinman, Tonia
Yarar, Defne
Bell, George W.
Cheeseman, Iain M
Date Issued
May 2014
Journal
Molecular Biology of the Cell
Publisher
American Society for Cell Biology
Citation
Thiru, P., D. M. Kern, K. L. McKinley, J. K. Monda, F. Rago, K.-C. Su, T. Tsinman, D. Yarar, G. W. Bell, and I. M. Cheeseman. “Kinetochore Genes Are Coordinately up-Regulated in Human Tumors as Part of a FoxM1-Related Cell Division Program.” Molecular Biology of the Cell 25, no. 13 (May 14, 2014): 1983–1994.
Version
Final published version
Abstract
The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA–microtubule interactions. Previous studies testing individual kinetochore genes documented examples of their overexpression in tumors relative to normal tissue, leading to proposals that up-regulation of specific kinetochore genes may promote tumor progression. However, kinetochore components do not function in isolation, and previous studies did not comprehensively compare the expression behavior of kinetochore components. Here we analyze the expression behavior of the full range of human kinetochore components in diverse published expression compendia, including normal tissues and tumor samples. Our results demonstrate that kinetochore genes are rarely overexpressed individually. Instead, we find that core kinetochore genes are coordinately regulated with other cell division genes under virtually all conditions. This expression pattern is strongly correlated with the expression of the forkhead transcription factor FoxM1, which binds to the majority of cell division promoters. These observations suggest that kinetochore gene up-regulation in cancer reflects a general activation of the cell division program and that altered expression of individual kinetochore genes is unlikely to play a causal role in tumorigenesis.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1091/mbc.E14-03-0837
