Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells

Shan Zhu, Lizhi Cao, Yan Yu, Liangchun Yang, Minghua Yang, Ke Liu, Jun Huang, Rui Kang, Kristen M. Livesey, Daolin Tang

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

IFN1@ (interferon, type 1, cluster, also called IFNa) has been extensively studied as a treatment for patients with chronic myeloid leukemia (CML). The mechanism of anticancer activity of IFN1@ is complex and not well understood. Here, we demonstrate that autophagy, a mechanism of cellular homeostasis for the removal of dysfunctional organelles and proteins, regulates IFN1@-mediated cell death. IFN1@ activated the cellular autophagic machinery in immortalized or primary CML cells. Activation of JAK1-STAT1 and RELA signaling were required for IFN1@-induced expression of BEC N1, a key regulator of autophagy. Moreover, pharmacological and genetic inhibition of autophagy enhanced IFN1@-induced apoptosis by activation of the CASP8-BID pathway. Taken together, these findings provide evidence for an important mechanism that links autophagy to immunotherapy in leukemia.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalAutophagy
Volume9
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Chronic Myeloid Leukemia
  • IFN1
  • Immunotherapy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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