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Aneuploidy acts both oncogenically and as a tumor suppressor
Beth A A Weaver1, Alain D Silk, Cristina Montagna
1Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cancer Cell
|December 27, 2006
Summary
Aneuploidy, or abnormal chromosome number, can drive tumor formation but also prevent it. Reduced CENP-E levels cause aneuploidy, revealing its complex role in cancer and chromosomal instability.
Area of Science:
- Cell biology
- Cancer research
- Genetics
Background:
- Aneuploidy (abnormal chromosome number) is a hallmark of cancer cells.
- Boveri's hypothesis linking aneuploidy to tumorigenesis remains largely untested due to challenges in its selective generation.
Purpose of the Study:
- To investigate the role of the mitosis-specific motor protein CENP-E in aneuploidy and tumorigenesis.
- To determine whether aneuploidy initiates or inhibits tumor formation.
Main Methods:
- Generating cells and mice with reduced levels of CENP-E.
- Assessing aneuploidy and chromosomal instability in vitro and in vivo.
- Evaluating tumor formation in aged animals and in chemically or genetically induced cancer models.
Main Results:
- Reduced CENP-E levels lead to aneuploidy and chromosomal instability.
- Increased aneuploidy drives spontaneous lymphoma and lung tumor formation in aged mice.
- Aneuploidy acts as a tumor suppressor in chemically or genetically induced cancer models.
Conclusions:
- Aneuploidy and chromosomal instability play a dual role in tumorigenesis, capable of both promoting and inhibiting cancer.
- The findings challenge the long-standing hypothesis that aneuploidy solely drives cancer initiation.
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