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1.
Cell ; 141(4): 583-94, 2010 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-20478252

RESUMO

Melanomas are highly heterogeneous tumors, but the biological significance of their different subpopulations is not clear. Using the H3K4 demethylase JARID1B (KDM5B/PLU-1/RBP2-H1) as a biomarker, we have characterized a small subpopulation of slow-cycling melanoma cells that cycle with doubling times of >4 weeks within the rapidly proliferating main population. Isolated JARID1B-positive melanoma cells give rise to a highly proliferative progeny. Knockdown of JARID1B leads to an initial acceleration of tumor growth followed by exhaustion which suggests that the JARID1B-positive subpopulation is essential for continuous tumor growth. Expression of JARID1B is dynamically regulated and does not follow a hierarchical cancer stem cell model because JARID1B-negative cells can become positive and even single melanoma cells irrespective of selection are tumorigenic. These results suggest a new understanding of melanoma heterogeneity with tumor maintenance as a dynamic process mediated by a temporarily distinct subpopulation.


Assuntos
Melanoma/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Histona Desmetilases com o Domínio Jumonji , Proteínas de Membrana/metabolismo , Camundongos , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Proteínas Nucleares/genética , Receptor Notch1/metabolismo , Proteínas Repressoras/genética , Proteínas Serrate-Jagged , Transdução de Sinais
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