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A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth.
- Source :
-
Cell [Cell] 2010 May 14; Vol. 141 (4), pp. 583-94. - Publication Year :
- 2010
-
Abstract
- 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.<br /> (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Calcium-Binding Proteins metabolism
Cell Line, Tumor
Cells, Cultured
Gene Knockdown Techniques
Humans
Intercellular Signaling Peptides and Proteins metabolism
Jumonji Domain-Containing Histone Demethylases
Membrane Proteins metabolism
Mice
Neoplasm Metastasis
Neoplastic Stem Cells metabolism
Nuclear Proteins genetics
Receptor, Notch1 metabolism
Repressor Proteins genetics
Serrate-Jagged Proteins
Signal Transduction
Melanoma metabolism
Nuclear Proteins metabolism
Repressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 141
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 20478252
- Full Text :
- https://doi.org/10.1016/j.cell.2010.04.020