自噬是真核生物中进化上保守的过程,它消除了有害成分并维持了一系列细胞外损伤的细胞内稳态。然而,这些侮辱可能会触发另一个突出的应激反应途径的下游信号,STAT3信号通路,这与自噬过程的多个方面有关。最近的报道进一步表明,STAT3的不同亚细胞定位模式以各种方式影响自噬。例如,核STAT3通过转录调控几个自噬相关基因,如BCL2家族成员,BECN1,PIK3C3,CTSB,CTSL,PIK3R1,HIF1A,BNIP3和具有自噬调节剂靶标的microRNA。细胞质STAT3通过螯合EIF2AK2以及通过与其他自噬相关信号分子如FOXO1和FOXO3相互作用来组成型抑制自噬。此外,STAT3的线粒体易位抑制氧化应激诱导的自噬,并可有效保护线粒体免于线粒体自噬的降解.了解STAT3信号传导在自噬调节中的作用可能有助于深入了解经典的自噬模型以及癌症治疗。特别是对于新兴的靶向治疗,因为一系列靶向药物通过阻断STAT3信号传导来执行抗肿瘤活性,这不可避免地影响自噬途径。这里,我们回顾了一些有代表性的研究和目前在这一特定领域的理解。
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.