title: Inhibiting autophagy potentiates the anticancer activity of IFN1@/IFNα in chronic myeloid leukemia cells.
abstract: 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.
authors.affiliation: Department of Pediatrics; Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.forename: Lizhi
authors.initials: L
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Liangchun
authors.initials: L
authors.lastname: Yang
authors.forename: Minghua
authors.initials: M
authors.lastname: Yang
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Livesey
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001343:Autophagy; D016923:Cell Death; D018922:HL-60 Cells; D006706:Homeostasis; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016898:Interferon-alpha / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000628:therapy*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; C498143:RELA protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051996:Transcription Factor RelA; C507904:JAK1 protein, human; D053613:Janus Kinase 1