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

30 Citations (Scopus)

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

Fingerprint

Autophagy
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon Type I
Organelles
Immunotherapy
Leukemia
Homeostasis
Cell Death
Pharmacology
Apoptosis
Proteins
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells. / Zhu, Shan; Cao, Lizhi; Yu, Yan; Yang, Liangchun; Yang, Minghua; Liu, Ke; Huang, Jun; Kang, Rui; Livesey, Kristen M.; Tang, Daolin.

In: Autophagy, Vol. 9, No. 3, 03.2013, p. 317-327.

Research output: Contribution to journalArticle

Zhu, S, Cao, L, Yu, Y, Yang, L, Yang, M, Liu, K, Huang, J, Kang, R, Livesey, KM & Tang, D 2013, 'Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells', Autophagy, vol. 9, no. 3, pp. 317-327. https://doi.org/10.4161/auto.22923
Zhu, Shan ; Cao, Lizhi ; Yu, Yan ; Yang, Liangchun ; Yang, Minghua ; Liu, Ke ; Huang, Jun ; Kang, Rui ; Livesey, Kristen M. ; Tang, Daolin. / Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells. In: Autophagy. 2013 ; Vol. 9, No. 3. pp. 317-327.
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AU - Liu, Ke

AU - Huang, Jun

AU - Kang, Rui

AU - Livesey, Kristen M.

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