The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma.
Commun Biol
; 5(1): 39, 2022 01 11.
Article
en En
| MEDLINE
| ID: mdl-35017636
ABSTRACT
High-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Ováricas
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Estrés Fisiológico
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Genes Supresores de Tumor
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Proteínas Serina-Treonina Quinasas
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Quinasas de la Proteína-Quinasa Activada por el AMP
Límite:
Female
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Humans
Idioma:
En
Revista:
Commun Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón