TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway.
Carcinogenesis
; 45(5): 324-336, 2024 May 19.
Article
em En
| MEDLINE
| ID: mdl-38267812
ABSTRACT
Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration both in vitro and in vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reduced O-glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment of N-acetyl-d-glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Carcinoma Pulmonar de Células não Pequenas
/
Proliferação de Células
/
Proteínas com Motivo Tripartido
/
Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)
/
Hexosaminas
/
Neoplasias Pulmonares
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article