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Succinylation Inhibits the Enzymatic Hydrolysis of the Extracellular Matrix Protein Fibrillin 1 and Promotes Gastric Cancer Progression

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机构： [1]Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China [2]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111, XianXia Road, Shanghai 200336, China [3]Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China [4]Department of Urology, Zhongda Hospital Affiliated to Southeastern China University, Nanjing 210029, China [5]Department of Biotherapy, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China [6]Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China

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关键词： fibrillin 1 gastric cancer MMP2 succinylation TGF-𝛽1

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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-β1 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.© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

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出版当年[2021]版：

大类 | 1 区

材料科学

小类 | 1 区纳米科技 1 区材料科学：综合 2 区化学综合

最新[2025]版：

大类 | 1 区

综合性期刊

小类 | 1 区化学：综合 1 区材料科学：综合 1 区纳米科技

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出版当年[2020]版：

Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 CHEMISTRY, MULTIDISCIPLINARY

最新[2023]版：

Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 14.3 最新[2023版] 16.3 最新五年平均 16.806 出版当年[2020版] 17.835 出版当年五年平均 15.84 出版前一年[2019版] 17.521 出版后一年[2021版]

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第一作者机构： [1]Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China [2]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111, XianXia Road, Shanghai 200336, China

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Succinylation Inhibits the Enzymatic Hydrolysis of the Extracellular Matrix Protein Fibrillin 1 and Promotes Gastric Cancer Progression

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