琥珀酰化
纤维蛋白
化学
细胞外基质
基质金属蛋白酶
细胞生物学
肿瘤进展
生物化学
生物
基因
乙酰化
作者
Xingyun Wang,Xiao Shi,Hongcheng Lu,Chen Zhang,Xiang Li,Tiancheng Zhang,Jiajia Shen,Jianxun Wen
标识
DOI:10.1002/advs.202200546
摘要
Abstract Extracellular matrix (ECM) remodeling is crucial in the regulation of gastric cancer (GC) progression. This work aims to reveal novel posttranslational modifications and their relevant mechanisms in GC. In 3D matrix culture and animal models, it is found that fibrillin 1 (FBN1) expression is increased in advanced GC and has succinylation modification. The succinylation modification of FBN1 blocks its degradation by matrix metalloproteinases (MMPs). The long‐term accumulation and deposition of FBN1 enhance tumor progression by activating TGF‐ β 1 and intracellular PI3K/Akt pathway. The FBN1 succinylation site monoclonal antibody can effectively intervene the effect of succinylation modification and inhibit GC progression. FBN1 is specifically upregulated in the progression of GC compared with other tumors. In conclusion, FBN1 is widely present in the form of K672‐succinylated modifications in GC. Besides, the succinyl group of FBN1 blocks its binding to MMP2, inhibits its degradation by MMP2, and leads to the accumulation of FBN1, which poses a long‐term risk to the poor prognosis of GC.
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