Journal
NATURE
Volume 467, Issue 7318, Pages 986-U168Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature09459
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Funding
- NCI [CA16672]
- American Cancer Society [RSG-07-082-01-MGO]
- Susan G. Komen Foundation [BCTR600208]
- Hildegardo E. and Olga M. Flores Foundation
- NCI-Cancer Center [CA-16672]
- Genitourinary Cancer SPORE [P50CA091846]
- Lung Cancer SPORE [P50CA070907, U01DE019765]
- Rita Allen Foundation
- V Foundation for Cancer Research
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Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours(1-6), but the mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
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