The Role of NEDD4-1 in Tumorigenesis of the Digestive System
10.13865/j.cnki.cjbmb.2021.05.1120
- Author:
Jun-Ze DAI
1
;
Yan JIN
1
;
Hai-Feng JIN
2
Author Information
1. Department of Cell Biology and Medical Genetics, College of Medicine, Yanbian University
2. Department of Internal Medicine, Affiliated Hospital of Yanbian University
- Publication Type:Journal Article
- Keywords:
developmentally down-regulated protein 4 (NEDD4-1);
digestive system;
E3 ubiquitin ligase;
malignant tumor;
neural precursor cell expressed;
ubiquitylation
- From:
Chinese Journal of Biochemistry and Molecular Biology
2022;38(4):410-417
- CountryChina
- Language:Chinese
-
Abstract:
Neural precursor cell Expressed‚Developmentally Down-regulated protein 4 (NEDD4-1‚ also known as NEDD4 in some papers) is a tumor-related protein that has attracted much attention in recent years. It belongs to the E3 HECT (homologous to E6 associated protein C terminus) ubiquitin ligase‚ which could ubiquitinate various proteins that are subsequently degraded in lysosomes or proteasomes‚ or mediate their nuclear-cytoplasmic translocation‚ or indirectly affect various signaling pathways of different malignant tumors. With the deepening of a large number of tumor-related experiments‚ it has been found that NEDD4-1 can affect the biological behavior of tumors by regulating cell cycle‚ invasion and metastasis of cancer cells‚ antagonize drug resistance and many other pathways. In digestive system tumors‚ NEDD4-1 mainly promotes the proliferation‚ invasion and migration of hepatocellular carcinoma through multiple pathways such as PTEN/ PI3K/ Akt‚ TGF-β‚ Hippo and LDLRAD4. In pancreatic cancer‚ NEDD4-1 acted as an oncogene in the PI3K/ Akt signaling pathway‚ but acted as a tumor suppressor gene in the Myc-Sirt2 signaling circuit. In gastric and colorectal cancer‚ the NEDD4-1-related signaling pathways are different from other digestive system tumors. NEDD4-1 promotes gastric cancer progression and metastasis (via the EGFR signaling pathway) and inhibits colorectal cancer tumor growth (via the Wnt signaling pathway) independently of the PTEN/ PI3K/ Akt pathway. NEDD4-1 has become a hot research direction for therapeutic purposes. In this paper‚ we summarize the functions‚ signaling pathways and potential inhibitors of NEDD4-1 in different digestive system tumors‚ and discuss the relationship between NEDD4-1 and different signaling pathways‚ aiming to provide important reference data for cancer therapy.
