Abstract
Abstract Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very low survival rates. Metastatic progression of tumors is the major cause of death in TNBC patients. Metastatic spread of tumor cells is generally associated with resistance to therapy and poor prognosis. Therefore, there is a clinical need for understanding the molecular and cellular basis of metastasis and developing effective therapies against metastatic progression. However, since metastasis is a multi-step process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor in TNBC, which acts as a homeostatic factor that regulates kinase activity. RKIP blocks invasion in vitro and experimental metastasis in vivo. Therefore, RKIP constitutes a powerful tool for studying metastatic signaling pathways in cancer cells. RKIP is known to regulate the activity of certain kinases such as Raf-1, GRK2, NIK, and GSK3β, affecting major pathways such as MAPK, NFκB, and WNT. However, our preliminary data suggests that RKIP affects a much larger part of the TNBC kinome. Using proteomics approaches, we have identified putative novel kinase targets of RKIP, and used bioinformatics analysis to build RKIP-regulated signaling networks. Elucidating RKIP's function at a systems level will reveal the interplay between key metastatic signaling cascades and potentially identify novel anti-metastatic target combinations in TNBCs. Citation Format: Ali E. Yesilkanal, Casey Frankenberger, Daniel Rabe, Gary L. Johnson, Marsha R. Rosner. Regulation of TNBC kinome by the metastasis suppressor Raf kinase inhibitory protein (RKIP). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3251. doi:10.1158/1538-7445.AM2015-3251
Published Version
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