Inhibition of the PLK1-Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Zhaoliang Yu
  • Peng Deng
  • Yufeng Chen
  • Shini Liu
  • Jinghong Chen
  • And 15 others
  • Zihuan Yang
  • Jianfeng Chen
  • Xinjuan Fan
  • Peili Wang
  • Zerong Cai
  • Yali Wang
  • Peishan Hu
  • Dezheng Lin
  • Rong Xiao
  • Yifeng Zou
  • Yan Huang
  • Qiang Yu
  • Ping Lan
  • Jing Tan
  • Xiaojian Wu

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Detail(s)

Original languageEnglish
Article number2100759
Journal / PublicationAdvanced Science
Volume8
Issue number23
Online published28 Oct 2021
Publication statusPublished - 8 Dec 2021

Link(s)

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.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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