Novel endogenous endoplasmic reticulum transmembrane protein SURF4 suppresses cell death by negatively regulating the STING-STAT6 axis in myeloid leukemia

[摘要] Myeloid differentiation was shown to be associated withreduced leukemic cell burden and leukemia-initiatingcells and improved survival [1]. Reactive oxygen species(ROS) are associated with leukemia and can induce endoplasmic reticulum (ER) stress. ER stress induces severalmechanisms, including cell death [2]. The stimulator ofinterferon genes (STING) is also an ER transmembraneprotein and promotes anti-tumor immunity by linkinginnate and adaptive immunity [3]. Signal transducer andactivator of transcription 6 (STAT6) plays a prominent rolein adaptive immunity by transducing signals from extracellular cytokines and inducing apoptosis in cancer cells [4].Surfeit 4 (SURF4) is a multi-pass ER transmembrane protein that participates in the ER-Golgi compartment, andSURF4 was found to be amplified and highly expressedin leukemic cells (Supplementary Figure S1A) and severalcancer types, including blood cancers [5]. STING interactswith STAT6 in the ER, and TANK-binding kinase 1 (TBK1)activates pSTAT6Y641, leading to anti-tumor effects in cancer cells [6]. Interestingly, SURF4 binds to STING [7], butit remains unclear how the STING-TBK1-STAT6 axis yieldsanti-tumor effects in blood cancers. The study methods aredetailed in the Supplementary Materials.

[学科分类] 社会科学、人文和艺术（综合）