TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Carcinogenesis - (2024) vom: 24. Jan.

Sprache:

Englisch

Beteiligte Personen:

Wei, Sisi [VerfasserIn]
Ai, Meiling [VerfasserIn]
Zhan, Yuan [VerfasserIn]
Yu, Jieqing [VerfasserIn]
Xie, Tao [VerfasserIn]
Hu, Qinghua [VerfasserIn]
Fang, Yang [VerfasserIn]
Huang, Xuan [VerfasserIn]
Li, Yong [VerfasserIn]

Links:

Volltext

Themen:

Glutamine fructose-6-phosphate amidotransferase 1 (GFAT1)
Hexosamine biosynthetic pathway (HBP)
Journal Article
Non-small-cell-lung carcinoma (NSCLC)
Tripartite Motif 14 (TRIM14)
Ubiquitination

Anmerkungen:

Date Revised 24.01.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1093/carcin/bgae005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367582341