An unexpected role for the ketogenic diet in triggering tumor metastasis by modulating BACH1-mediated transcription.
Sci Adv
; 10(23): eadm9481, 2024 Jun 07.
Article
en En
| MEDLINE
| ID: mdl-38838145
ABSTRACT
We have found that the ketogenic (Keto) diet is able to, unexpectedly, promote the metastatic potential of cancer cells in complementary mouse models. Notably, the Keto diet-induced tumor metastasis is dependent on BTB domain and CNC homolog 1 (BACH1) and its up-regulation of pro-metastatic targets, including cell migration-inducing hyaluronidase 1, in response to the Keto diet. By contrast, upon genetic knockout or pharmacological inhibition of endogenous BACH1, the Keto diet-mediated activation of those targets is largely diminished, and the effects on tumor metastasis are completely abolished. Mechanistically, upon administration of the Keto diet, the levels of activating transcription factor 4 (ATF4) are markedly induced. Through direct interaction with BACH1, ATF4 is recruited to those pro-metastatic target promoters and enhances BACH1-mediated transcriptional activation. Together, these data implicate a distinct transcription regulatory program of BACH1 for tumor metastasis induced by the Keto diet. Our study also raises a potential health risk of the Keto diet in human patients with cancer.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico
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Dieta Cetogénica
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Metástasis de la Neoplasia
Límite:
Animals
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article