Inhibition of the PLK1-Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Article number | 2100759 |
Journal / Publication | Advanced Science |
Volume | 8 |
Issue number | 23 |
Online published | 28 Oct 2021 |
Publication status | Published - 8 Dec 2021 |
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DOI | DOI |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85120958358&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(4d0da8da-0ff9-452c-83b8-00ec214e2074).html |
Abstract
Dysregulation of the cell cycle machinery leads to genomic instability and is a hallmark of cancer associated with chemoresistance and poor prognosis in colorectal cancer (CRC). Identifying and targeting aberrant cell cycle machinery is expected to improve current therapies for CRC patients. Here,upregulated polo-like kinase 1 (PLK1) signaling, accompanied by deregulation of cell cycle-related pathways in CRC is identified. It is shown that aberrant PLK1 signaling correlates with recurrence and poor prognosis in CRC patients. Genetic and pharmacological blockade of PLK1 significantly increases the sensitivity to oxaliplatin in vitro and in vivo. Mechanistically, transcriptomic profiling analysis reveals that cell cycle-related pathways are activated by oxaliplatin treatment but suppressed by a PLK1 inhibitor. Cell division cycle 7 (CDC7) is further identified as a critical downstream effector of PLK1 signaling, which is transactivated via the PLK1-MYC axis. Increased CDC7 expression is also found to be positively correlated with aberrant PLK1 signaling in CRC and is associated with poor prognosis. Moreover, a CDC7 inhibitor synergistically enhances the anti-tumor effect of oxaliplatin in CRC models, demonstrating the potential utility of targeting the PLK1-MYC-CDC7 axis in the treatment of oxaliplatin-based chemotherapy.
Research Area(s)
- cell division cycle 7, colorectal cancer, MYC, oxaliplatin, polo-like kinase 1
Citation Format(s)
Inhibition of the PLK1-Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer. / Yu, Zhaoliang; Deng, Peng; Chen, Yufeng et al.
In: Advanced Science, Vol. 8, No. 23, 2100759, 08.12.2021.
In: Advanced Science, Vol. 8, No. 23, 2100759, 08.12.2021.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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