Roles of tumor suppressors (TSs) in metastatic progression

Division Of Basic Sciences - Nci

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Abstract

Our studies demonstrate that tumor suppressors are often silenced during metastatic progression through epigenetic mechanisms (e.g., promoter hypermethylation and histone modification). TS deregulation promotes the acquisition of plasticity and the ability of tumor cells to adapt to hostile tissue microenvironments, thus facilitating metastatic spread. We use integrated genome-wide genetic and epigenetic approaches to investigate the role of TSs during metastatic progression and the underlying mechanisms involving host inflammatory and immune responses. Our studies uncover a novel mechanism in which inactivation of TSs promotes a non-cell-autonomous inflammatory regulation and alters immune landscape of tumor-bearing host.