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

IFN1@ (interferon, type 1, cluster, also called IFNα) 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 homeostas...

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Published in:Autophagy 2013-03, Vol.9 (3), p.317-327
Main Authors: Zhu, Shan, Cao, Lizhi, Yu, Yan, Yang, Liangchun, Yang, Minghua, Liu, Ke, Huang, Jun, Kang, Rui, Livesey, Kristen M., Tang, Daolin
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Autophagy
Basic Research Paper
Cell Death
chronic myeloid leukemia
HL-60 Cells
Homeostasis
Humans
IFN1@
immunotherapy
Immunotherapy - methods
Interferon-alpha - pharmacology
Janus Kinase 1 - metabolism
Jurkat Cells
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy
Signal Transduction
STAT1 Transcription Factor - metabolism
Transcription Factor RelA - metabolism
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Summary:IFN1@ (interferon, type 1, cluster, also called IFNα) 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 BECN1, 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.
ISSN:1554-8627
1554-8635
DOI:10.4161/auto.22923