The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway.
Cell Death Dis
; 15(7): 466, 2024 Jul 02.
Article
de En
| MEDLINE
| ID: mdl-38956029
ABSTRACT
Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteurs de transcription
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Mouvement cellulaire
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Tumeurs du rhinopharynx
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Protéines adaptatrices de la transduction du signal
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Facteurs de transcription ARNTL
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Cancer du nasopharynx
/
Angiomotines
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Protéines de signalisation YAP
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Souris nude
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Invasion tumorale
Limites:
Animals
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Female
/
Humans
/
Male
Langue:
En
Journal:
Cell Death Dis
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine