| 项目编号 | PRJCA009896 | ||||||||
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| 项目标题 | Lymphotoxin-β Promotes Breast Cancer Bone Metastasis Colonization and Dormancy Reactivation | ||||||||
| 涉及领域 | Medical | ||||||||
| 数据类型 |
Transcriptome or Gene expression
Raw sequence reads Single cell sequencing |
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| 物种名称 | Mus musculus | ||||||||
| 描述信息 | Bone metastasis is a common complication of breast cancer. Understanding the molecular mechanisms governing bone metastatic dormancy and the awakening are of vital importance to develop therapeutic intervention strategies. By utilizing experimental mouse models for bone metastasis and single cell sequencing technology, we systematically analyzed the single cell transcriptomes of tumor cells during bone metastasis colonization. The transcriptomes of early seeding cells are significantly different from late-stage bone metastasis cells, and even more distinct from that of cell culture or primary tumors. An in vivo cDNA library screen of genes which are highly expressed in early-stage bone metastatic cells is performed. Several candidate genes are enriched in the assay. With additional confirmation experiments, Lymphotoxin-β (LTβ) stands out as a major bone-metastasis promoting gene, with its expression negatively correlates with breast cancer bone metastasis-free survival. Importantly, LTβ promotes a previously known bone metastatic dormant cell line to generate overtly late-stage bone metastasis. Mechanistically, tumor cells are induced to express LTβ in the bone, mostly through TGF-β signaling that is enriched in the osteoblastic niche. Tumor-derived LTβ then activates the NF-kB signaling in the osteoblasts to release CCL2/5, which feeds back to tumor cells to promote their seeding and outgrowth. These findings reveal LTβ as a bone niche signaling induced factor to promote tumor cell seeding and dormancy outbreak in the bone. LTβ is a potential therapeutic target to prevent the bone metastasis dormancy outgrowth. | ||||||||
| 样品范围 | Multiisolate | ||||||||
| 发布日期 | 2024-06-04 | ||||||||
| 项目资金来源 |
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| 提交者 | Hanqiu Zheng (hanzheng@mail.tsinghua.edu.cn) | ||||||||
| 提交单位 | Tsinghua University | ||||||||
| 提交日期 | 2022-06-04 |