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The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells
Abstract
In papillary thyroid carcinomas (PTCs), rearrangements of the RET receptor (RET/PTC) and activating mutations in the BRAF or RAS oncogenes are mutually exclusive. Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation. Adoptive activation of the RET/PTC-RAS-BRAF axis induced cell proliferation and Matrigel invasion of thyroid follicular cells. Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion. Thus, motile and mitogenic properties are intrinsic to transformed thyroid cells and are governed by an epistatic oncogenic signaling cascade.
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Cited by
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Zhang, B., Pan, X., Cobb, G. P., & Anderson, T. A. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.028 · Cited by 2,749
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Antonelli, A., Ferrari, S. M., Giuggioli, D., Ferrannini, E., Ferri, C., & Fallahi, P. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.10.010 · Cited by 595
Schweppe, R. E., Klopper, J. P., Korch, C., Pugazhenthi, U., Benezra, M., Knauf, J. A., Fagin, J. A., Marlow, L. A., Copland, J. A., Smallridge, R. C., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1102 · Cited by 563
Riesco-Eizaguirre, G., Rodríguez, I., De la Vieja, A., Costamagna, E., Carrasco, N., Nistal, M., & Santisteban, P. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1248 · Cited by 265
Bommarito, A., Richiusa, P., Carissimi, E., Pizzolanti, G., Rodolico, V., Zito, G., Criscimanna, A., Di Blasi, F., Pitrone, M., Zerilli, M., et al. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0076 · Cited by 70
Metadata
- Authors
- Melillo, R. M., Castellone, M. D., Guarino, V., De Falco, V., Cirafici, A. M., Salvatore, G., Caiazzo, F., Basolo, F., Giannini, R., Kruhoffer, M., Orntoft, T., Fusco, A., & Santoro, M.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-03-10
- Volume
- 115
- Issue
- 4
- Pages
- 1068-1081
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4247134666
- Cited by
- 242
- References
- 0
- FWCI
- 15.69
- Type
- journal article
- Language
- en
- Open access
- closed
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- Melillo, R. M., Castellone, M. D., Guarino, V., De Falco, V., Cirafici, A. M., Salvatore, G., Caiazzo, F., Basolo, F., Giannini, R., Kruhoffer, M., Orntoft, T., Fusco, A., & Santoro, M. (2005). The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci200522758
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