CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells

Q Wang1, J Ma1, Y Lu1

  • 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Oncogene
|May 24, 2017
PubMed

Insights

Cell cycle-related kinase 20 (CDK20) enhances lung cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Radiochemoresistance drives lung cancer recurrence and metastasis.
  • Mechanisms underlying radiochemoresistance are not fully understood.
  • Cell cycle-related kinase 20 (CDK20) is implicated in cancer cell growth.

Purpose of the Study:

  • To investigate the role of CDK20 in lung cancer radiochemoresistance.
  • To elucidate the molecular mechanisms by which CDK20 influences radiochemoresistance.

Main Methods:

  • Tandem affinity purification to identify CDK20 interacting proteins.
  • Immunostaining to assess CDK20 expression in lung cancer tissues.
  • Cell proliferation assays, G2/M arrest analysis, and radiochemosensitivity testing following CDK20 depletion.

Main Results:

  • CDK20 binds to Kelch-like ECH-associated protein 1 (KEAP1), a regulator of nuclear factor erythroid-2-related factor 2 (NRF2).
  • CDK20 enhances NRF2 transcriptional activity, reduces reactive oxygen species, and promotes cell proliferation and G2/M arrest.
  • CDK20 depletion increases lung cancer cell sensitivity to radiochemotherapy, partly via NRF2 inactivation.
  • CDK20 is overexpressed in human lung cancer tissues.

Conclusions:

  • CDK20 promotes lung cancer progression and radiochemoresistance by modulating the KEAP1-NRF2 pathway.
  • CDK20 represents a potential therapeutic target for overcoming lung cancer radiochemoresistance.

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