Journal
CANCER CELL
Volume 20, Issue 1, Pages 92-103Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2011.05.025
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Funding
- American Cancer Society
- National Institutes of Health Training
- FCT [Praxis XXI/BD/21794/99]
- KWF
- NIH [RO1 CA93947, U01 CA84313, P50 CA93683]
- Melanoma Research Foundation
- American Skin Association
- Fundação para a Ciência e a Tecnologia [PRAXIS XXI/BD/21794/99] Funding Source: FCT
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Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this deterministic hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.
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