Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3ß.
Mol Endocrinol
; 26(11): 1808-20, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-23002080
ABSTRACT
Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3ß (GSK3ß), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3ß phosphorylation. Melatonin activates GSK3ß by inhibiting the serine-threonine kinase Akt phosphorylation, inducing ß-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3ß activity and driving epithelial-to-mesenchymal transition in breast cancer patients.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Ritmo Circadiano
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Glucógeno Sintasa Quinasa 3
/
Transición Epitelial-Mesenquimal
/
Melatonina
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Endocrinol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Año:
2012
Tipo del documento:
Article