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

doi:10.4161/auto.22923

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 journal › Article › peer-review

45 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 language	English (US)
Pages (from-to)	317-327
Number of pages	11
Journal	Autophagy
Volume	9
Issue number	3
DOIs	https://doi.org/10.4161/auto.22923
State	Published - Mar 2013
Externally published	Yes

Keywords

Apoptosis
Autophagy
Chronic Myeloid Leukemia
IFN1
Immunotherapy

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.4161/auto.22923

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title = "Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells",

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.",

keywords = "Apoptosis, Autophagy, Chronic Myeloid Leukemia, IFN1, Immunotherapy",

author = "Shan Zhu and Lizhi Cao and Yan Yu and Liangchun Yang and Minghua Yang and Ke Liu and Jun Huang and Rui Kang and Livesey, {Kristen M.} and Daolin Tang",

note = "Funding Information: We thank Christine Heiner (Department of Surgery/Department of Anesthesiology, University of Pittsburgh) for editing work. This work was supported by grants from the National Natural Sciences Foundation of China (30973234 and 31171328 to L.C.), a grant from the University of Pittsburgh (D.T.), and grants from the National Institutes of Health (R01CA160417 to D.T.).",

year = "2013",

month = mar,

doi = "10.4161/auto.22923",

language = "English (US)",

volume = "9",

pages = "317--327",

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T1 - Inhibiting autophagy potentiates the anticancer activity of IFN1/IFNα in chronic myeloid leukemia cells

AU - Zhu, Shan

AU - Cao, Lizhi

AU - Yu, Yan

AU - Yang, Liangchun

AU - Yang, Minghua

AU - Liu, Ke

AU - Huang, Jun

AU - Kang, Rui

AU - Livesey, Kristen M.

AU - Tang, Daolin

N1 - Funding Information: We thank Christine Heiner (Department of Surgery/Department of Anesthesiology, University of Pittsburgh) for editing work. This work was supported by grants from the National Natural Sciences Foundation of China (30973234 and 31171328 to L.C.), a grant from the University of Pittsburgh (D.T.), and grants from the National Institutes of Health (R01CA160417 to D.T.).

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

KW - Apoptosis

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KW - Chronic Myeloid Leukemia

KW - IFN1

KW - Immunotherapy

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

Abstract

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ASJC Scopus subject areas

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