期刊
DEVELOPMENTAL CELL
卷 56, 期 17, 页码 2440-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2021.07.006
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资金
- Italian Association for Cancer Research (MFAG 2018) [21665]
- Fondazione Cariplo
- MIUR
- Italian Ministry of Health [531000]
- Dutch Cancer Society grant [2017-RUG-11457]
- Azrieli Foundation
- Israel Cancer Association [20200111]
- Israel Cancer Research Fund (Gesher Award)
- Dod CDMRP Career Development Award [CA191148]
- United States -Israel Binational Science Foundation [2019228]
- HFSP grant
- City of Paris
- Ricerca Finalizzata [GR-2018-12367077]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [2019228] Funding Source: National Science Foundation
Mitotic errors causing aneuploidy can lead to genome instability, affecting gene copy number and influencing cancer cells' resistance to chemotherapy. This may explain why some chemotherapy treatments fail.
Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.
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