Roles of tumor suppressors (TSs) in metastatic progression

我们的研究表明，肿瘤抑制因子通常在转移过程中通过表观遗传机制（如启动子超甲基化和组蛋白修饰）沉默。解除TS调控可促进肿瘤细胞获得可塑性和适应不良组织微环境的能力，从而促进转移性扩散。我们使用整合的全基因组遗传和表观遗传学方法来研究TSs在转移进展中的作用以及涉及宿主炎症和免疫反应的潜在机制。我们的研究揭示了TSs失活促进非细胞自主炎症调节和改变荷瘤宿主免疫景观的新机制。

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.