Related Experiment Video

Updated: Jun 30, 2025

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

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AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine

Bing Deng1, Fang Liu1, Nana Chen1

  • 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Cell Death & Disease
|March 24, 2024
PubMed

Insights

Aurora Kinase A (AURKA) inhibition targets amino acid synthesis vulnerabilities in KEAP1-deficient non-small cell lung cancer (NSCLC). This study identifies a new therapeutic strategy for difficult-to-treat NSCLC by linking AURKA to amino acid metabolism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Aurora Kinase A (AURKA) is a validated cancer target, but its inhibitors show variable efficacy across tumor types.
  • KEAP1-deficient non-small cell lung cancer (NSCLC) presents therapeutic challenges due to resistance to standard treatments.

Purpose of the Study:

  • To investigate the role of AURKA in amino acid synthesis and its therapeutic potential in KEAP1-deficient NSCLC.
  • To identify specific metabolic vulnerabilities associated with AURKA inhibition in NSCLC.

Main Methods:

  • CRISPR metabolic screening to identify drug sensitivities.
  • In vitro and in vivo experiments to assess the efficacy of AURKA inhibitor MLN8237.
  • Mechanistic studies involving protein interactions and phosphorylation.
  • Analysis of amino acid biosynthesis pathways, including ASNS expression.

Main Results:

  • KEAP1-knockdown NSCLC cells exhibit heightened sensitivity to the AURKA inhibitor MLN8237.
  • AURKA regulates amino acid synthesis via the GCN2-eIF2α-ATF4 pathway.
  • AURKA inhibition suppresses asparagine synthetase (ASNS) expression, crucial for KEAP1-deficient NSCLC survival.
  • NRF2 activation mediates the response to AURKA inhibition in KEAP1-deficient NSCLC.

Conclusions:

  • AURKA plays a critical role in regulating amino acid metabolism, particularly in KEAP1-deficient NSCLC.
  • The study identifies a novel metabolic vulnerability and a specific indication for AURKA inhibitors in NSCLC.
  • Targeting AURKA offers a promising therapeutic strategy for KEAP1-mutant/deficient NSCLC, addressing resistance to existing therapies.

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