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ST6GALNAC1介导非小细胞肺癌中黏蛋白的唾液酸化以逃避免疫监视。

ST6GALNAC1 mediates sialylation of mucins in non-small cell lung cancer to evade immune surveillance.

作者信息

Fu Ting, Wang Yanan, Wang Ling, Mao Yanqing

机构信息

Department of General Practice, The Fourth Affiliated Hospital of Soochow University, Suzhou, China.

Department of General Practice, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

J Thorac Dis. 2025 Aug 31;17(8):6076-6089. doi: 10.21037/jtd-2025-660. Epub 2025 Aug 28.

DOI:10.21037/jtd-2025-660
PMID:40950850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433114/
Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) ranks first among common cancers worldwide and first among causes of cancer death. This study explored the function of ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 1 (ST6GALNAC1) on immune surveillance in NSCLC.

METHODS

All the samples (patients with NSCLCs) were immediately snap frozen in liquid nitrogen and stored at -80 ℃ for further using. Mice were randomly divided into two groups. And functional verification was performed in combination with quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay, western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay and transwell co-culture system.

RESULTS

We found that ST6GALNAC1 expression in patients with NSCLC were up-regulated. Overall survival (OS) and disease-free survival (DFS) of patients with ST6GALNAC1 up-regulation were lower than those of patients with ST6GALNAC1 down-regulation. In mice model of NSCLC, ST6GALNAC1 promoted cancer cell growth and immune surveillance. ST6GALNAC1 promoted the invasion and migration of NSCLCs. ST6GALNAC1 promotes ferroptosis of macrophage. ST6GALNAC1 suppressed p-Akt expression of macrophage to promote ferroptosis of macrophage. Akt agonists reduced the effects of ST6GALNAC1 on immune surveillance.

CONCLUSIONS

Together, these results show that ST6GALNAC1 evades immune surveillance in NSCLC by Akt, suggesting that targeting ST6GALNAC1 may reduce ferroptosis of macrophage in NSCLCs. This infers that ST6GALNAC1 is potential target to be used in the treatment of NSCLCs.

摘要

背景

非小细胞肺癌（NSCLC）在全球常见癌症中位居首位，在癌症死亡原因中也位居首位。本研究探讨了ST6 N-乙酰半乳糖胺α-2,6-唾液酸转移酶1（ST6GALNAC1）在NSCLC免疫监视中的作用。

方法

所有样本（NSCLC患者）立即在液氮中速冻，并储存在-80℃以备进一步使用。小鼠被随机分为两组。并结合定量聚合酶链反应（qPCR）、酶联免疫吸附测定、蛋白质免疫印迹法、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）增殖试验和Transwell共培养系统进行功能验证。

结果

我们发现NSCLC患者中ST6GALNAC1表达上调。ST6GALNAC1上调患者的总生存期（OS）和无病生存期（DFS）低于ST6GALNAC1下调患者。在NSCLC小鼠模型中，ST6GALNAC1促进癌细胞生长和免疫监视。ST6GALNAC1促进NSCLC的侵袭和迁移。ST6GALNAC1促进巨噬细胞的铁死亡。ST6GALNAC1抑制巨噬细胞的p-Akt表达以促进巨噬细胞的铁死亡。Akt激动剂降低了ST6GALNAC1对免疫监视的影响。

结论

总之，这些结果表明ST6GALNAC1通过Akt逃避NSCLC中的免疫监视，提示靶向ST6GALNAC1可能减少NSCLC中巨噬细胞的铁死亡。这推断ST6GALNAC1是用于治疗NSCLC的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/1688181e7e8f/jtd-17-08-6076-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/4b99e2cbcc71/jtd-17-08-6076-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/62a152794302/jtd-17-08-6076-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/473de40b4fa5/jtd-17-08-6076-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/02061e7ac188/jtd-17-08-6076-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/334b72f0de4c/jtd-17-08-6076-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/0cf919cd6722/jtd-17-08-6076-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/545ea952fcc1/jtd-17-08-6076-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/012c694d2db8/jtd-17-08-6076-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/da5e26649738/jtd-17-08-6076-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/1688181e7e8f/jtd-17-08-6076-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/4b99e2cbcc71/jtd-17-08-6076-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/62a152794302/jtd-17-08-6076-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/473de40b4fa5/jtd-17-08-6076-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/02061e7ac188/jtd-17-08-6076-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/334b72f0de4c/jtd-17-08-6076-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/0cf919cd6722/jtd-17-08-6076-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/545ea952fcc1/jtd-17-08-6076-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/012c694d2db8/jtd-17-08-6076-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/da5e26649738/jtd-17-08-6076-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6591/12433114/1688181e7e8f/jtd-17-08-6076-f10.jpg

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