De novo lipogenesis protects dormant breast cancer cells from ferroptosis and promotes metastasis
Dormant disseminated tumor cells (DTCs) remain viable for years to decades before establishing a clinically overt metastatic lesion. DTCs are known to be highly resilient and able to overcome the multiple biological hurdles imposed along the metastatic cascade. However, the specific metabolic adapta...
| Autores: | , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:dnet:digitalcsic_::c351c8b778f871f893bc994b7822697f |
| Acesso em linha: | http://hdl.handle.net/10261/427972 https://api.elsevier.com/content/abstract/scopus_id/85214337189 |
| Access Level: | acceso abierto |
| Palavra-chave: | Breast cancer Ferroptosis Lipid metabolism Lipid peroxidation Metastasis Monounsaturated fatty acids activation Tumor cell dormancy |
| Resumo: | Dormant disseminated tumor cells (DTCs) remain viable for years to decades before establishing a clinically overt metastatic lesion. DTCs are known to be highly resilient and able to overcome the multiple biological hurdles imposed along the metastatic cascade. However, the specific metabolic adaptations of dormant DTCs remain to be elucidated. Here, we reveal that dormant DTCs upregulate de novo lipogenesis and favor the activation and incorporation of monounsaturated fatty acids (MUFAs) to their cellular membranes through the activation of acyl-coenzyme A synthetase long-chain family member 3 (ACSL3). Pharmacologic inhibition of de novo lipogenesis or genetic knockdown of ACSL3 results in lipid peroxidation and non-apoptotic cell death through ferroptosis. Clinically, ACSL3 was found to be overexpressed in quiescent DTCs in the lymph nodes of breast cancer patients and to significantly correlate with shorter disease-free and overall survival. Our work provides new insights into the molecular mechanisms enabling the survival of dormant DTCs and supports the use of de novo lipogenesis inhibitors to prevent breast cancer metastasis. |
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