Abstract 4998: NFAT signaling modulates tumor microenvironment.

Abstract Nuclear factor of activated T cells (NFAT) transcription factors regulate several cancer-related processes, such as migration and invasion. We have shown that NFAT is both necessary and sufficient to drive invasive migration of breast carcinoma cells. NFAT target genes that contribute to this phenotype encode cyclo-oxygenase-2, the enzyme required for the production of prostaglandin E2, and autotaxin, which catalyzes the synthesis of lysophosphatidic acid. NFAT also promotes tumor progression downstream of vascular endothelial growth factors and contributes to angiogenesis and lymphangiogenesis, though the underlying molecular mechanisms that control these phenotypes have remained unknown. In our present studies, we have identified novel NFAT target genes whose products are likely to modify tumor microenvironment through paracrine signaling to immune cells. We have generated stable pools of breast cancer cells with inducible lentiviral silencing or overexpression of NFAT and performed quantitative real-time RT-PCR to identify NFAT-responsive genes that code for soluble factors. This approach yielded several novel candidates, including those encoding cytokines and chemokines. The contribution of these NFAT-regulated gene products to tumor-stromal interactions is currently under investigation. Our studies propose a central role for NFAT in modulating tumor microenvironment. Citation Format: Aura Kaunisto, Alex Toker. NFAT signaling modulates tumor microenvironment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4998. doi:10.1158/1538-7445.AM2013-4998