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Abstract

A gain-of-function retroviral cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces solitary mammary carcinoma cells, which have disseminated to others sites and undergone an extended period of dormancy, to exit from dormancy at lung metastatic sites. Evidence indicates that Coco awakens tumor progenitor cells that have extravasated into the lung by inhibiting stroma-derived Bone Morphogenetic Proteins (BMP). Whereas Coco enhances the manifestation of traits associated with cancer stem cells, activation of canonical BMP signaling suppresses these processes. Expression of Coco correlates with lung metastatic capacity in a number of human breast cancer cell lines and induces a gene expression signature that predicts metastatic relapse to the lung but not to the bone in advanced primary tumors. Disclosed herein is the gain-of-function retroviral cDNA screen and a gene signature predictive of selective relapse and gene expression microarrays or panels based thereon for use in prognostication of relapse.

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