Journal
CANCER RESEARCH
Volume 70, Issue 12, Pages 5096-5108Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-4148
Keywords
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Funding
- Breast Specialized Program of Research Excellence (SPORE) [CA116199]
- Ovarian SPORE [CA83639]
- DOD [COE W81WXH-06-2-0033]
- National Breast Cancer Foundation, Inc.
- National Science Council, Taiwan [NSC-96-3111-B]
- China Medical University and Hospital-M. D. Anderson Cancer Center
- NIH [CCSG CA16672]
- Cancer Center Research of Excellence (Taiwan) [DOH-TD-C-111-005]
- National Science Council [NSC 96-2320-B-004-MY2, NSC 97-2320-B-039-039-MY3, NSC 98-2815-C-039-082-B]
- National Science Council of Taiwan [TMS-094-2-B-023]
- National Health Research Institutes [NHRI-EX97-9712BC]
- Department of Health, Taiwan [DOH97-TD-G111-024]
- China Medical University [CMU96-220, CMU96-189, CMU97-277]
- M.D. Anderson Cancer Center
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The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A -> miRNA-520h -> PP2A/C -> I kappa B kinase. NF-kappa B -> Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression. Cancer Res; 70(12); 5096-108. (C) 2010 AACR.
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