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Identification of Aneuploidy-Selective Antiproliferation Compounds

Tang, Yun-Chi, Williams, Bret R., Siegel, Jake J., Amon, Angelika·2011·Cell
DOI 10.1016/j.cell.2011.01.017
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Abstract

Aneuploidy, an incorrect chromosome number, is a hallmark of cancer. Compounds that cause lethality in aneuploid, but not euploid, cells could therefore provide new cancer therapies. We have identified the energy stress-inducing agent AICAR, the protein folding inhibitor 17-AAG, and the autophagy inhibitor chloroquine as exhibiting this property. AICAR induces p53-mediated apoptosis in primary mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19. AICAR and 17-AAG, especially when combined, also show efficacy against aneuploid human cancer cell lines. Our results suggest that compounds that interfere with pathways that are essential for the survival of aneuploid cells could serve as a new treatment strategy against a broad spectrum of human tumors.

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  • A HaloTag-p62 (SQSTM1) chimera can be covalently labeled with HaloTag ligands, and loss of signal can be monitored without interference by subsequent changes in protein synthesis.

    “One solution to problems relating to variations in SQSTM1 expression levels is to use a HaloTag ® -p62 (SQSTM1) chimera [585].The chimeric protein can be covalently labeled with HaloTag ® ligands, and the loss of signal can then be monitored without interference by subsequent changes in protein synthesis.”

    From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [585]

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Metadata

Authors
Tang, Y.-C., Williams, B. R., Siegel, J. J., & Amon, A.
Venue
Cell
Publisher
Elsevier BV
Published
2011-02
Volume
144
Issue
4
Pages
499-512
ISSN
0092-8674
DOI
10.1016/j.cell.2011.01.017
Cited by
328
References
9
Language
en
Licence

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