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Updated: Feb 12, 2026

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AP-1 confers resistance to anti-cancer therapy by activating XIAP

Yuan Wang1, Guo-Hui Wan1, Ying-Min Wu1

  • 1Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Oncotarget
|March 28, 2018
PubMed

Insights

Histone deacetylase (HDAC) inhibitors can cause cancer drug resistance by increasing XIAP. This occurs through activating AP-1, a mechanism linked to poor outcomes in breast and liver cancers.

Area of Science:

  • Molecular Oncology
  • Cancer Drug Resistance
  • Epigenetics

Background:

  • Intrinsic and acquired resistance to chemotherapy are primary causes of treatment failure in cancer patients.
  • Histone deacetylase (HDAC) inhibitors represent a promising therapeutic strategy, but their resistance mechanisms are not well understood.

Purpose of the Study:

  • To elucidate the resistance mechanisms induced by HDAC inhibitors.
  • To investigate the role of XIAP and AP-1 in HDAC inhibitor-mediated chemo-drug resistance.

Main Methods:

  • Treatment of cancer cells with a specific HDAC inhibitor (JNJ-2648158).
  • Analysis of gene transcription, including XIAP and AP-1 components like c-Fos.
  • Correlation of molecular findings with clinical outcomes in breast and liver cancer patient cohorts.

Main Results:

  • The HDAC inhibitor JNJ-2648158 induced XIAP transcription by activating AP-1.
  • High expression of c-Fos, induced by the HDAC inhibitor, promoted AP-1 formation.
  • This mechanism conferred resistance to chemotherapeutics and was associated with poor clinical outcomes in breast and liver cancers.

Conclusions:

  • A novel mechanism of chemo-drug resistance involving HDAC inhibitors, XIAP, and AP-1 has been identified.
  • XIAP may represent a potential therapeutic target for overcoming chemo-drug resistance in specific cancers.
  • Targeting this pathway could improve treatment efficacy in chemo-resistant breast and liver cancers.
Keywords:
AP-1HDAC inhibitorJNJ26481585XIAPdrug resistant

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