The goal of the proposed study is to elucidate and identify the signal transduction pathways that are important in mediating malignant cell transformation of the oncogenic receptor protein tyrosine kinase (RPTK) Ros which was originally discovered as the oncogene of an avian sarcoma virus called UR2. The PTK domain of Ros shares high homology with those of insulin and insulin-like growth factor I receptors (IR and IGFR). However, the physiological function of Ros appears to be rather different than those of IR and IGFR. The focus of this study will be to identify specific signaling pathways and molecules required for the distinct cell transforming functions of Ros. The major approach will employ loss-of- function mutants of Ros as well as various activated and dominant inhibitory mutants of signaling molecules to dissect the signal transduction pathways of Ros.
The specific aims are: l. To establish mutant Ros expressing mammalian cell lines and to characterize their biological and biochemical properties. 2. To elucidate the role ofRho/Rac1/Cdc42-mediated signaling pathways in Ros-induced cell growth and transformation. 3. To explore the role of IRS-1 and PI3 kinase in Ros-induced cell growth and transformation. 4. To inquire the role of cytoskeletal protein-mediated signaling in Ros- induced cell growth and transformation. 5. To assess the role of IGF-I receptor in Ros-induced cell growth and transformation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Virology Study Section (VR)
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Read-Connole, Elizabeth Lee
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Mount Sinai School of Medicine
Schools of Medicine
New York
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Schlosshauer, Peter W; Li, Wei; Lin, Kai-Ti et al. (2009) Rapamycin by itself and additively in combination with carboplatin inhibits the growth of ovarian cancer cells. Gynecol Oncol 114:516-22
Zhang, Weizhou; Cheng, George Zhi; Gong, Jianli et al. (2008) RACK1 and CIS mediate the degradation of BimEL in cancer cells. J Biol Chem 283:16416-26
Cheng, George Z; Zhang, Wei Zhou; Sun, Mei et al. (2008) Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem 283:14665-73
Cheng, George Z; Park, Sungman; Shu, Shaokun et al. (2008) Advances of AKT pathway in human oncogenesis and as a target for anti-cancer drug discovery. Curr Cancer Drug Targets 8:2-6
Cheng, George Z; Zhang, Weizhou; Wang, Lu-Hai (2008) Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay. Cancer Res 68:957-60
Uttamsingh, S; Bao, X; Nguyen, K T et al. (2008) Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene 27:2626-34
Cheng, George Z; Chan, Joseph; Wang, Qi et al. (2007) Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res 67:1979-87
Wang, Lu-Hai; Chan, Joseph L-K; Li, Wei (2007) Rapamycin together with herceptin significantly increased anti-tumor efficacy compared to either alone in ErbB2 over expressing breast cancer cells. Int J Cancer 121:157-64
Zhang, Weizhou; Zong, Cong S; Hermanto, Ulrich et al. (2006) RACK1 recruits STAT3 specifically to insulin and insulin-like growth factor 1 receptors for activation, which is important for regulating anchorage-independent growth. Mol Cell Biol 26:413-24
Wang, Lu-Hai (2004) Molecular signaling regulating anchorage-independent growth of cancer cells. Mt Sinai J Med 71:361-7

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