Loss of PICH promotes chromosome instability and cell death in triple-negative breast cancer
| Autor: | Jiaqi Wu, Yan Huang, Tao Li, Jiang-Man Zhao, Ailing Li, Qiu-Ying Han, Luye Lv, Weiwei Yan, Xiaomin Ying, Yuan Chen, Xiaohong Yao, Qing Xia, Xuemin Zhang, Tian Xia, Feng Gu, Liang Chen, Teng Li, Wan-Jin Li, Ming Zhao, Tao Zhou |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Cell Survival Immunology Transplantation Heterologous Mice Nude Apoptosis Triple Negative Breast Neoplasms Article Metastasis 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Breast cancer Chromosome instability Chromosomal Instability medicine Animals Humans lcsh:QH573-671 Neoplasm Metastasis Mitotic catastrophe Triple-negative breast cancer Cell Proliferation lcsh:Cytology business.industry DNA Helicases Cell Biology medicine.disease Prognosis Chromatin Transplantation 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Cancer research MCF-7 Cells Female business |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 6, Pp 1-13 (2019) |
| ISSN: | 2041-4889 |
| Popis: | Triple-negative breast cancer (TNBC), defined by the lack of expression of estrogen, progesterone, and ERBB2 receptors, has the worst prognosis of all breast cancers. It is difficult to treat owing to a lack of effective molecular targets. Here, we report that the growth of TNBC cells is exceptionally dependent on PICH, a DNA-dependent ATPase. Clinical samples analysis showed that PICH is highly expressed in TNBC compared to other breast cancer subtypes. Importantly, its high expression correlates with higher risk of distal metastasis and worse clinical outcomes. Further analysis revealed that PICH depletion selectively impairs the proliferation of TNBC cells, but not that of luminal breast cancer cells, in vitro and in vivo. In addition, knockdown of PICH in TNBC cells induces the formation of chromatin bridges and lagging chromosomes in anaphase, frequently resulting in micronucleation or binucleation, finally leading to mitotic catastrophe and apoptosis. Collectively, our findings show the dependency of TNBC cells on PICH for faithful chromosome segregation and the clinical potential of PICH inhibition to improve treatment of patients with high-risk TNBC. |
| Databáze: | OpenAIRE |
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