UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP.
10.1016/j.apsb.2024.09.005
- Author:
Andi ZHAO
1
;
Chenyu ZHOU
1
;
Jinjing LI
1
;
Zijin WANG
1
;
Hui ZHU
1
;
Shiya SHEN
1
;
Qing SHAO
1
;
Qi GONG
1
;
Hu LIU
1
;
Xuejuan CHEN
1
Author Information
1. Department of Ophthalmology, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
- Publication Type:Journal Article
- Keywords:
Hypoxia;
Invasion and metastasis;
LGALS3BP;
Tumor microenvironment;
UBE2G2;
Ubiquitination;
Uveal melanoma;
Vasculogenic mimicry
- From:
Acta Pharmaceutica Sinica B
2024;14(12):5201-5218
- CountryChina
- Language:English
-
Abstract:
Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeutic strategies for UM.
