The spontaneous development of cutaneous melanomas in Tyr-Ras+ transgenic mice on INK4a +1- and INK4a-/- backgrounds established a causal role of activated RAS in the pathogenesis of melanoma. The requirement for continuous RAS activation to maintain the viability of established tumors in the inducible Tyr/Tet-Ras+ INK4a-/-system demonstrated a critical and essential role for activated RAS in maintenance of melanomas. However, this RAS-INK4a melanoma model fails to recapitulate an important hallmark of the human disease - metastasis. It is this 'deficiency' that renders the RAS-INK4a model uniquely suitable for the discovery, characterization and validation of metastasis pathways. In this proposal, we will generate of a novel melanoma model in which the candidate progression gene, Met, can be regulated somatically in established RAS-induced non-metastatic melanomas. The impact of MET activation (and deactivation) will be examined on phenotypic, molecular/genetic and genomic levels to validate a role for MET in progression, and ultimately to delineate genes and pathways critically important for tumor progression, and possibly metastasis
| Wardwell-Ozgo, J; Dogruluk, T; Gifford, A et al. (2014) HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome. Oncogene 33:1017-26 |
| Kwong, Lawrence N; Heffernan, Timothy P; Chin, Lynda (2013) A systems biology approach to personalizing therapeutic combinations. Cancer Discov 3:1339-44 |
| Cheng, Christine S; Rai, Kunal; Garber, Manuel et al. (2013) Semiconductor-based DNA sequencing of histone modification states. Nat Commun 4:2672 |
| Hodis, Eran; Watson, Ian R; Kryukov, Gregory V et al. (2012) A landscape of driver mutations in melanoma. Cell 150:251-63 |
| Tsao, Hensin; Chin, Lynda; Garraway, Levi A et al. (2012) Melanoma: from mutations to medicine. Genes Dev 26:1131-55 |
| Scott, Kenneth L; Nogueira, Cristina; Heffernan, Timothy P et al. (2011) Proinvasion metastasis drivers in early-stage melanoma are oncogenes. Cancer Cell 20:92-103 |
| Nogueira, C; Kim, K-H; Sung, H et al. (2010) Cooperative interactions of PTEN deficiency and RAS activation in melanoma metastasis. Oncogene 29:6222-32 |
| Kabbarah, Omar; Nogueira, Cristina; Feng, Bin et al. (2010) Integrative genome comparison of primary and metastatic melanomas. PLoS One 5:e10770 |
| Scott, Kenneth L; Chin, Lynda (2010) Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis. Clin Cancer Res 16:2229-34 |
| Zheng, Bin; Jeong, Joseph H; Asara, John M et al. (2009) Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell 33:237-47 |
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