» Articles » PMID: 35901491

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

Overview
Journal Adv Sci (Weinh)
Date 2022 Jul 28
PMID 35901491
Authors
Affiliations
Soon will be listed here.
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-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.

Citing Articles

Unlocking the Hidden Potential of Cancer Therapy Targeting Lysine Succinylation.

Zheng Z, Xiao P, Kuang J, Wang Z, Wang X, Huang D J Cancer. 2025; 16(3):821-834.

PMID: 39781339 PMC: 11705062. DOI: 10.7150/jca.105849.


Mechanistic insights into SIRT7 and EZH2 regulation of cisplatin resistance in bladder cancer cells.

Cao Y, Wang S, Ma J, Long M, Ma X, Yang X Cell Death Dis. 2024; 15(12):931.

PMID: 39719443 PMC: 11668892. DOI: 10.1038/s41419-024-07321-1.


SIRT5 participates in the suppressive tumor immune microenvironment of EGFR-mutant LUAD by regulating the succinylation of ACAT1.

Shouhan W, Qingchang L, Xiaodan S Heliyon. 2024; 10(21):e39743.

PMID: 39524872 PMC: 11543872. DOI: 10.1016/j.heliyon.2024.e39743.


Phenotypic Heterogeneity of Patients With Marfan Syndrome in Puerto Rico: A Case Series.

Jimenez-Berrios G, Vazquez-Folch S, Izquierdo N Cureus. 2024; 16(9):e68791.

PMID: 39376868 PMC: 11456412. DOI: 10.7759/cureus.68791.


Huangqi-Danshen Decoction Against Renal Fibrosis in UUO Mice via TGF-β1 Induced Downstream Signaling Pathway.

Huang X, Peng Y, Lu L, Gao L, Wu S, Lu J Drug Des Devel Ther. 2024; 18:4119-4134.

PMID: 39296670 PMC: 11410030. DOI: 10.2147/DDDT.S457100.


References
1.
Boyd N, Martin L, Yaffe M, Minkin S . Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Res. 2011; 13(6):223. PMC: 3326547. DOI: 10.1186/bcr2942. View

2.
Oudin M, Jonas O, Kosciuk T, Broye L, Guido B, Wyckoff J . Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression. Cancer Discov. 2016; 6(5):516-31. PMC: 4854754. DOI: 10.1158/2159-8290.CD-15-1183. View

3.
Jain R . Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol. 2013; 31(17):2205-18. PMC: 3731977. DOI: 10.1200/JCO.2012.46.3653. View

4.
Marigo I, Trovato R, Hofer F, Ingangi V, Desantis G, Leone K . Disabled Homolog 2 Controls Prometastatic Activity of Tumor-Associated Macrophages. Cancer Discov. 2020; 10(11):1758-1773. DOI: 10.1158/2159-8290.CD-20-0036. View

5.
Zhang Z, Tan M, Xie Z, Dai L, Chen Y, Zhao Y . Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol. 2010; 7(1):58-63. PMC: 3065206. DOI: 10.1038/nchembio.495. View