TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway
TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway
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DOI：
10.1093/carcin/bgae005
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发表时间：
2024-01-24
期刊：
影响因子：
4.7
通讯作者：
Li，Yong
中科院分区：
文献类型：
--
作者：
Wei，Sisi;Ai，Meiling;Li，Yong
TRIM 14是属于E3连接酶TRIM家族的癌蛋白，其参与除非小细胞肺癌（NSCLC）之外的多种肿瘤的进展。然而，目前对TRIM 14在NSCLC中的功能和相关机制知之甚少。本研究发现TRIM 14蛋白在肺腺癌组织中表达较癌旁组织下调，在体外和体内均能抑制肿瘤细胞的增殖和迁移。此外，TRIM 14可以直接结合谷氨酰胺果糖-6-磷酸酰胺转移酶1（GFAT 1），这反过来导致GFAT 1的降解和O-糖基化水平降低。GFAT 1是氨基己糖生物合成途径（HBP）限速步骤中的关键酶。补充N-乙酰-D-氨基葡萄糖可成功逆转TRIM 14对NSCLC细胞生长和迁移的抑制作用。总的来说，我们的数据显示，TRIM 14通过泛素化和降解GFAT 1抑制NSCLC细胞增殖和迁移，为TRIM 14对HBP提供了新的调节作用。
Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration bothin vitroandin vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reducedO-glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment ofN-acetyl-d-glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP.