The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis
Open accessAbstract
Smad4/ DPC4 (deleted in pancreatic carcinoma, locus 4) is a tumor suppressor gene lost at high frequency in cancers of the pancreas and other gastrointestinal organs. Smad4 encodes a key intracellular messenger in the transforming growth factor β (TGF-β) signaling cascade. TGF-β is a potent inhibitor of the growth of epithelial cells; thus, it has been assumed that loss of Smad4 during tumor progression relieves this inhibition. Herein, we show that restoration of Smad4 to human pancreatic carcinoma cells suppressed tumor formation in vivo , yet it did not restore sensitivity to TGF-β. Rather, Smad4 restoration influenced angiogenesis, decreasing expression of vascular endothelial growth factor and increasing expression of thrombospondin-1. In contrast to the parental cell line and to control transfectants that produced rapidly growing tumors in vivo , Smad4 revertants induced small nonprogressive tumors with reduced vascular density. These data define the control of an angiogenic switch as an alternative, previously unknown mechanism of tumor suppression for Smad4 and identify the angiogenic mediators vascular endothelial growth factor and thrombospondin-1 as key target genes.
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Cites
DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1
Hahn, S. A., Schutte, M., Shamsul Hoque, A. T. M., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., et al. (1996) · Science · doi:10.1126/science.271.5247.350 · Cited by 2,337
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Cited by
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
TGF-β Signaling in Tumor Suppression and Cancer Progression
Derynck, R., Akhurst, R. J., & Balmain, A. (2001) · Nature Genetics · doi:10.1038/ng1001-117 · Cited by 2,275
Bardeesy, N., Cheng, K.-H., Berger, J. H., Chu, G. C., Pahler, J., Olson, P., Hezel, A. F., Horner, J., Lauwers, G. Y., Hanahan, D., et al. (2006) · Genes & Development · doi:10.1101/gad.1478706 · Cited by 674
Syed, V. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25496 · Cited by 482
(2001) · PubMed · Cited by 309
Metadata
- Authors
- Schwarte-Waldhoff, I., Volpert, O. V., Bouck, N. P., Sipos, B., Hahn, S. A., Klein-Scory, S., Lüttges, J., Klöppel, G., Graeven, U., Eilert-Micus, C., Hintelmann, A., & Schmiegel, W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-08-15
- Volume
- 97
- Issue
- 17
- Pages
- 9624-9629
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2015353751
- Cited by
- 266
- References
- 1
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- green
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- Schwarte-Waldhoff, I., Volpert, O. V., Bouck, N. P., Sipos, B., Hahn, S. A., Klein-Scory, S., Lüttges, J., Klöppel, G., Graeven, U., Eilert-Micus, C., Hintelmann, A., & Schmiegel, W. (2000). Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.97.17.9624
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