Proteomic Mapping and Targeting of Mitotic Pericentriolar Material in Tumors Bearing Centrosome Amplification
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Abstract
Recent work has made it clear that pericentriolar material (PCM), the matrix of proteins surrounding centrioles, contributes to most functions of centrosomes. Given the occurrence of centrosome amplification in most solid tumors and the unconventional survival of these tumor cells, it is tempting to hypothesize that gel-like mitotic PCM would cluster extra centrosomes to defend against mitotic errors and increase tumor cell survival. However, because PCM lacks an encompassing membrane, is highly dynamic, and is physically connected to centrioles, few methods can decode the components of this microscale matrix. In this study, we took advantage of differential labeling between two sets of APEX2-centrosome reactions to design a strategy for acquiring the PCM proteome in living undisturbed cells without synchronization treatment, which identified 392 PCM proteins. Localization of ubiquitination promotion proteins away from PCM was a predominant mechanism to maintain the large size of PCM for centrosome clustering during mitosis in cancer cells. Depletion of PCM gene kinesin family member 20A (KIF20A) caused centrosome clustering failure and apoptosis in cancer cells in vitro and in vivo. Thus, our study suggests a strategy for targeting a wide range of tumors exhibiting centrosome amplification and provides a proteomic resource for future mining of PCM proteins. Significance: This study identifies the proteome of pericentriolar material and reveals therapeutic vulnerabilities in tumors bearing centrosome amplification.
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- Authors
- Xie, B., Pu, Y., Yang, F., Chen, W., Yue, W., Ma, J., Zhang, N., Jiang, Y., Wu, J., Lin, Y., Liang, X., Wang, C., Zou, P., & Li, M.
- Affiliations
- Peking University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Center for Life Sciences (CN)
- Corresponding author
- Zou, Peng
- Li, Mo
- ORCID
- Venue
- Cancer Research
- Published
- 2022-05-27
- Volume
- 82
- Issue
- 14
- Pages
- 2576-2592
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W4282936934
- Cited by
- 12
- References
- 6
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81871160, 81521002, 32088101, 21727806, 32100554)
- Ministry of Science and Technology (2018YFA0507600, 2017YFA0503600)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- pericentriolar material, centrosome amplification, mitosis, ubiquitination, KIF20A, centrosome clustering, cancer therapy targets, tumor cell survival
- MeSH terms
- Centrioles, Humans, Mitosis, Centrosome, Proteome, Proteomics
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