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吡啉抑制FAS介导的细胞凋亡以支持结直肠癌存活。

Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival.

作者信息

Ma Huanhuan, Suleman Muhammad, Zhang Fengqiong, Cao Tingyan, Wen Shixiong, Sun Dachao, Chen Lili, Jiang Bin, Wang Yue, Lin Furong, Wang Jinyang, Li Boan, Li Qinxi

机构信息

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, 361102, China.

出版信息

Adv Sci (Weinh). 2024 Mar;11(10):e2301476. doi: 10.1002/advs.202301476. Epub 2023 Dec 26.

DOI:10.1002/advs.202301476
PMID:38148593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10933653/
Abstract

Resistance to immunotherapy in colorectal cancer (CRC) is associated with obstruction of FAS (Apo-1 or CD95)-dependent apoptosis, a hallmark of cancer. Here it is demonstrated that the upregulation of pirin (PIR) protein in colon cancers promotes tumorigenesis. Knockout or inhibition of PIR dramatically increases FAS expression, FAS-dependent apoptosis and attenuates colorectal tumor formation in mice. Specifically, NFκB2 is a direct transcriptional activator of FAS and robustly suppressed by PIR in dual mechanisms. One is the disruption of NFκB2 complex (p52-RELB) association with FAS promoter, the other is the inhibition of NIK-mediated NFκB2 activation and nuclear translocation, leading to the inability of active NFκB2 complex toward the transcription of FAS. Furthermore, PIR interacts with FAS and recruits it in cytosol, preventing its membrane translocation and assembling. Importantly, knockdown or knockout of PIR dramatically sensitizes cells to FAS mAb- or active CD8 T cells-triggered cell death. Taken together, a PIR-NIK-NFκB2-FAS survival pathway is established, which plays a key role in supporting CRC survival.

摘要

结直肠癌（CRC）对免疫疗法的耐药性与FAS（Apo-1或CD95）依赖性凋亡的受阻有关，这是癌症的一个标志。本文证明结肠癌中pirin（PIR）蛋白的上调促进肿瘤发生。敲除或抑制PIR可显著增加FAS表达、FAS依赖性凋亡，并减弱小鼠结直肠肿瘤的形成。具体而言，NFκB2是FAS的直接转录激活因子，并在双重机制中受到PIR的强烈抑制。一种机制是NFκB2复合物（p52-RELB）与FAS启动子的结合被破坏，另一种机制是抑制NIK介导的NFκB2激活和核转位，导致活性NFκB2复合物无法转录FAS。此外，PIR与FAS相互作用并将其募集到细胞质中，阻止其膜转位和组装。重要的是，敲低或敲除PIR可显著使细胞对FAS单克隆抗体或活性CD8 T细胞触发的细胞死亡敏感。综上所述，建立了一条PIR-NIK-NFκB2-FAS生存途径，该途径在支持CRC生存中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/4a84f5225de8/ADVS-11-2301476-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/b1ca55171506/ADVS-11-2301476-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/4548fccfceaf/ADVS-11-2301476-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/4a84f5225de8/ADVS-11-2301476-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/5f9f29c20172/ADVS-11-2301476-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/243ed111b549/ADVS-11-2301476-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/10933653/7318869b92e4/ADVS-11-2301476-g003.jpg
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3
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