title: The role of STAT3 in autophagy.
abstract: Autophagy is an evolutionarily conserved process in eukaryotes that eliminates harmful components and maintains cellular homeostasis in response to a series of extracellular insults. However, these insults may trigger the downstream signaling of another prominent stress responsive pathway, the STAT3 signaling pathway, which has been implicated in multiple aspects of the autophagic process. Recent reports further indicate that different subcellular localization patterns of STAT3 affect autophagy in various ways. For example, nuclear STAT3 fine-tunes autophagy via the transcriptional regulation of several autophagy-related genes such as BCL2 family members, BECN1, PIK3C3, CTSB, CTSL, PIK3R1, HIF1A, BNIP3, and microRNAs with targets of autophagy modulators. Cytoplasmic STAT3 constitutively inhibits autophagy by sequestering EIF2AK2 as well as by interacting with other autophagy-related signaling molecules such as FOXO1 and FOXO3. Additionally, the mitochondrial translocation of STAT3 suppresses autophagy induced by oxidative stress and may effectively preserve mitochondria from being degraded by mitophagy. Understanding the role of STAT3 signaling in the regulation of autophagy may provide insight into the classic autophagy model and also into cancer therapy, especially for the emerging targeted therapy, because a series of targeted agents execute antitumor activities via blocking STAT3 signaling, which inevitably affects the autophagy pathway. Here, we review several of the representative studies and the current understanding in this particular field.
authors.affiliation: a Department of Medical Oncology; Zhejiang University ; Hangzhou , Zhejiang , China.
authors.forename: Liangkun
authors.initials: L
authors.lastname: You
authors.forename: Zhanggui
authors.initials: Z
authors.lastname: Wang
authors.forename: Hongsen
authors.initials: H
authors.lastname: Li
authors.forename: Jiawei
authors.initials: J
authors.lastname: Shou
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jing
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
authors.forename: Xinbing
authors.initials: X
authors.lastname: Sui
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor
keywords: ALK, anaplastic lymphoma receptor tyrosine kinase; ATF4, activating transcription factor 4; BNIP3, BCL2/adenovirus E1B 19kDa interacting protein 3; CNTF, ciliary neurotrophic factor; COX8, cytochrome c oxidase subunit VIII; CTSB, cathepsin B; CTSL, cathepsin L; CYCS, cytochrome c, somatic; ConA, concanavalin A; CuB, cucurbitacin B; EGF, epidermal growth factor; EIF2A, eukaryotic initiation factor 2A, 65kDa; EIF2AK2, eukaryotic translation initiation factor 2-α kinase 2; ER, endoplasmic reticulum; ETC, electron transport chain; FOXO1/3, forkhead box O1/3; HDAC3, histone deacetylase 3; HIF1A, hypoxia inducible factor 1, α subunit (basic helix-loop-helix transcription factor); IL6, interleukin 6; IMM, inner mitochondrial membrane; KDR, kinase insert domain receptor; LMP, lysosomal membrane permeabilization; MAP1LC3A, microtubule-associated protein 1 light chain 3 α; MAPK1, mitogen-activated protein kinase 1; MLS, mitochondrial localization sequence; MMP14, matrix metallopeptidase 14 (membrane-inserted); NDUFA13, NADH dehydrogenase (ubiquinone) 1 α subcomplex, 13; NES, nuclear export signal; NFKB1, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; NLS, nuclear localization signal; PDGFRB, platelet-derived growth factor receptor, β polypeptide; PRKAA2, protein kinase, AMP-activated, α 2 catalytic subunit; PTPN11, protein tyrosine phosphatase, non-receptor type 11; PTPN2, protein tyrosine phosphatase, non-receptor type 2; PTPN6, protein tyrosine phosphatase, non-receptor type 6; ROS, reactive oxygen species; RTK, receptor tyrosine kinases; SH2, src homology 2; STAT3; STAT3, signal transducer and activator of transcription 3 (acute-phase response factor); VHL, von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase; XPO1, exportin 1; autophagy; cancer; miRNA, microRNA; mitoSTAT3, mitochondrial STAT3; mitophagy; receptor tyrosine kinases; targeted therapy