Journal
NATURE
Volume 541, Issue 7635, Pages 41-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature20791
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Funding
- European Research Council (ERC)
- Government of Cataluna
- Fundacion Botin and Banco Santander, through Santander Universities
- Worldwide Cancer Research
- Beug Stiftung Foundation
- La Caixa International
- EU Cofound postdoctoral fellowship
- Spanish 'Ministerio de Educacion y Ciencia' [SAF2013-48926-P]
- European Commission's 7th Framework Program 4DCellFate grant [277899]
- Severo Ochoa Award of Excellence from MINECO (Government of Spain)
- ICREA Funding Source: Custom
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The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44(bright) cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36(+) metastasis- initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36(+) metastasis- initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis- initiating cells particularly rely on dietary lipids to promote metastasis.
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