CKAP2L, transcriptionally inhibited by FOXP3, promotes breast carcinogenesis through the AKT/mTOR pathway.
Exp Cell Res
; 412(2): 113035, 2022 03 15.
Article
en En
| MEDLINE
| ID: mdl-35065924
ABSTRACT
Cytoskeleton-associated protein 2-like (CKAP2L) is a mitotic spindle protein and its high expression is reported to be associated with the poor prognosis of cancer patients. Interestingly, TNMplot website analysis indicated that CKAP2L expression was significantly higher in breast cancer (BC) tissues than in normal breast tissues (P < 0.001). Thus, this study was conducted to investigate the role of CKAP2L in breast carcinogenesis and its underlying molecular mechanisms. The mRNA and protein expression levels of CKAP2L in 40 paired fresh BC and para-carcinoma specimens were first analyzed, and the results confirmed the high expression of CKAP2L in BC tissues. Functional studies revealed that CKAP2L silencing dramatically suppressed the proliferation, migration, and invasion, induced cell cycle arrest and apoptosis of BC cells in vitro, and inhibited the growth of xenografted tumors in vivo. However, CKAP2L overexpression produced the opposite results. Mechanically, CKAP2L could activate the AKT/mTOR signaling pathway in BC cells accompanied by increased phosphorylation levels of AKT, mTOR, and p70S6K in CKAP2L-overexpressed cells. Forkhead box protein P3 (FOXP3), a transcription factor with tumor-suppressive properties, was proved to negatively regulate CKAP2L expression in BC cells through binding to the promoter of CKAP2L and inhibiting its transcription. In summary, the present study demonstrates that CKAP2L, transcriptionally regulated by FOXP3, activates the AKT/mTOR signaling pathway and promotes breast carcinogenesis. CKAP2L may serve as a promising target of therapeutic intervention for BC.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Neoplasias de la Mama
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Transformación Celular Neoplásica
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Proteínas del Citoesqueleto
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Proteínas Proto-Oncogénicas c-akt
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Factores de Transcripción Forkhead
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Serina-Treonina Quinasas TOR
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article