Majority of cancer patients will die of metastases originating from disseminated tumor cells (DTCs), years or even decades after treatment. This suggests that DTCs survive in a dormant, nonproliferative state. However, because the biology of DTCs is poorly understood it is critical to ask basic mechanistic questions to further develop translational approaches. Our goal is to identify these mechanisms by combining powerful In vivo models and novel imaging and nano-device technologies available through this collaboration. This consortium provides unprecedented synergy to study dormancy and address three emphasis areas of this RFA: 1) tumor dormancy, activation of dormant cells and the tumor microenvironment (SAI), and dormancy in response to cancer treatment (SA2);2) imaging the tumor microenvironment during tumor metastasis, and dormancy (SAI), as well as in response to therapies (SA2) and 3) characterization and functional relevance of the tumor microenvironment extracellular matrix (ECM) and how tumor cells stroma interactions (i.e. niches) establish metastatic cell fate (SA2). We hypothesize that at least two scenarios influence DTC dormancy. Scenario 1: DTCs from invasive cancers activate stress signals in response to a growth-restrictive target organ microenvironment inducing dormancy. Scenario 2: therapy and/or microenvironmental stress conditions (e.g. hypoxia) acfing on primary tumor cells carrying a

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We will use novel imaging and nano-device technologies to tag, track and isolate disseminating tumor cells departing from primary tumors and proliferating or entering dormancy in target organs. We will discover their metabolic, genomic and transcription profiles to identity a cancer dormancy gene signature relevant to patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-3)
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Albert Einstein College of Medicine
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Curran, Colleen S; Carrillo, Esteban R; Ponik, Suzanne M et al. (2015) Collagen density regulates xenobiotic and hypoxic response of mammary epithelial cells. Environ Toxicol Pharmacol 39:114-24
Sosa, María Soledad; Bragado, Paloma; Aguirre-Ghiso, Julio A (2014) Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer 14:611-22
Chéry, Lisly; Lam, Hung-Ming; Coleman, Ilsa et al. (2014) Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways. Oncotarget 5:9939-51
Roh-Johnson, M; Bravo-Cordero, J J; Patsialou, A et al. (2014) Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation. Oncogene 33:4203-12
Avivar-Valderas, A; Wen, H C; Aguirre-Ghiso, J A (2014) Stress signaling and the shaping of the mammary tissue in development and cancer. Oncogene 33:5483-90
Lopez-Rivera, Esther; Jayaraman, Padmini; Parikh, Falguni et al. (2014) Inducible nitric oxide synthase drives mTOR pathway activation and proliferation of human melanoma by reversible nitrosylation of TSC2. Cancer Res 74:1067-78
Kwon, Mijung; Lee, Soo Jin; Wang, Yarong et al. (2014) Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis. Int J Cancer 135:48-60
Sosa, Maria Soledad; Bragado, Paloma; Debnath, Jayanta et al. (2013) Regulation of tumor cell dormancy by tissue microenvironments and autophagy. Adv Exp Med Biol 734:73-89
Begley, Ulrike; Sosa, Maria Soledad; Avivar-Valderas, Alvaro et al. (2013) A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-*. EMBO Mol Med 5:366-83
Aguirre-Ghiso, Julio A; Bragado, Paloma; Sosa, Maria Soledad (2013) Metastasis awakening: targeting dormant cancer. Nat Med 19:276-7

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