ASPM promotes migration and invasion of anaplastic thyroid carcinoma by stabilizing KIF11.
Cell Biol Int
; 47(7): 1209-1221, 2023 Jul.
Article
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| MEDLINE
| ID: mdl-36883909
ABSTRACT
Abnormal spindle-like microcephaly-associated (ASPM) protein is crucial to the mitotic spindle function during cell replication and tumor progression in multiple tumor types. However, the effect of ASPM in anaplastic thyroid carcinoma (ATC) has not yet been understood. The present study is to elucidate the function of ASPM in the migration and invasion of ATC. ASPM expression is incrementally upregulated in ATC tissues and cell lines. Knockout (KO) of ASPM pronouncedly attenuates the migration and invasion of ATC cells. ASPM KO significantly reduces the transcript levels of Vimentin, N-cadherin, and Snail and increases E-cadherin and Occludin, thereby inhibiting epithelial-to-mesenchymal transition (EMT). Mechanistically, ASPM regulates the movement of ATC cells by inhibiting the ubiquitin degradation of KIF11 and thus stabilizing it via direct binding to it. Moreover, xenograft tumors in nude mice proved that KO of ASPM could ameliorate tumorigenesis and tumor growth accompanied by a decreased protein expression of KIF11 and an inhibition of EMT. In conclusion, ASPM is a potentially useful therapeutic target for ATC. Our results also reveal a novel mechanism by which ASPM inhibits the ubiquitin process in KIF11.
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Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
/
Carcinoma Anaplásico de Tiroides
Límite:
Animals
/
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article