Inhibiting autophagy potentiates the anticancer activity of IFN1α/IFNα in chronic myeloid leukemia cells

被引：47

作者：

Zhu, Shan ^{[1
]}

Cao, Lizhi ^{[1
]}

Yu, Yan ^{[1
]}

Yang, Liangchun ^{[1
]}

Yang, Minghua ^{[1
]}

Liu, Ke ^{[3
]}

Huang, Jun ^{[4
]}

Kang, Rui ^{[5
]}

Livesey, Kristen M. ^{[5
]}

Tang, Daolin ^{[2
,5
]}

机构：

[1] Cent South Univ, Dept Pediat, Xiangya Hosp, Changsha, Hunan, Peoples R China

[2] Cent South Univ, Dept Infect Dis, Xiangya Hosp, Changsha, Hunan, Peoples R China

[3] Cent South Univ, Dept Ophthalmol, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[4] Cent South Univ, Dept Orthopaed, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[5] Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, Pittsburgh, PA USA

来源：

AUTOPHAGY | 2013年 / 9卷 / 03期

基金：

美国国家卫生研究院;

关键词：

IFN1@; autophagy; apoptosis; immunotherapy; chronic myeloid leukemia; ALPHA-INDUCED APOPTOSIS; IFN-ALPHA; TARGETING AUTOPHAGY; REGULATES AUTOPHAGY; BCR-ABL; INTERFERON-ALPHA; BLADDER-CANCER; EXPRESSION; DEATH; RESISTANCE;

D O I：

10.4161/auto.22923

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

IFN1@ (interferon, type 1, cluster, also called IFN alpha) 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.

引用

页码：317 / 327

页数：11

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