Roles of tumor suppressors (TSs) in metastatic progression

肿瘤抑制因子（TS）在转移进展中的作用

• 批准号: 10926149
• 负责人: Li Yang
• 金额: $ 90.08万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926149
• 关键词: Cell Proliferation; Cell Survival; Cells; Epigenetic Process; Genetic; Genetic Transcription; Hypermethylation; Immune; Immune response; Inflammatory; Inflammatory Response; Oncogenes; Play; Regulation; Role; Signal Transduction; Tissues; Tumor Suppressor Proteins; genome-wide; growth promoting activity; histone modification; neoplastic cell; novel; promoter; tumor; tumor-immune system interactions

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.

我们的研究表明，肿瘤抑制基因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)被沉默。TS的去调控促进了肿瘤细胞的可塑性和适应敌对组织微环境的能力，从而促进了转移扩散。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在转移过程中的作用以及涉及宿主炎症和免疫反应的潜在机制。我们的研究揭示了一种新的机制，即TSS的失活促进了非细胞自主的炎症调节，并改变了荷瘤宿主的免疫格局。

项目成果

Microenvironment: Making connections.

微观环境：建立联系。

• DOI: 10.1038/nrc3492
• 发表时间: 2013
• 期刊: Nature reviews. Cancer
• 作者: Seton-Rogers,Sarah

DNA Methyltransferase 3B-Mediated Intratumoral Heterogeneity and Therapeutic Targeting in Breast Cancer Recurrence and Metastasis.

• DOI: 10.1158/1541-7786.mcr-21-0887
• 发表时间: 2022-11-03
• 期刊: Molecular cancer research : MCR

Roles of tumor suppressors in regulating tumor-associated inflammation.

• DOI: 10.1038/cdd.2014.131
• 发表时间: 2014-11
• 期刊: Cell death and differentiation
• 影响因子: 12.4

Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling.

• DOI: 10.1371/journal.pgen.1003251
• 发表时间: 2013
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Achyut BR;Bader DA;Robles AI;Wangsa D;Harris CC;Ried T;Yang L
• 通讯作者: Yang L