Identification of a minority population of LMO2+ breast cancer cells that integrate into the vasculature and initiate metastasis.

Metastasis is responsible for the majority of breast cancer-related deaths, however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1+/VEGFA+ tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher abundance of LMO2+ basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by TNFα and IL6. Collectively, our study identifies a population of metastasis-initiating ..., Brief overview
Please find enclosed in this repository two main folders:
(1) 'data', which contains raw and processed data used for the genomic analysis done in the manuscript including original scRNA-seq data from our laboratory and publicly available scRNA-seq data from other labs, and
(2) 'scripts', which contains the code and scripts used to generate the results shown in the figures. Please reach out directly to us if you have any questions about the data and scripts enclosed here for the manuscript., All data are stored as tab-delimited text files that can be opened with any spreadsheet software program. All code was written in either R or bash.Â

转移是绝大多数乳腺癌相关死亡的主要原因，但长期以来，鉴定肿瘤转移的细胞决定因素始终颇具挑战。本研究在人类乳腺肿瘤活检样本中，鉴定出一小群未成熟的THY1+/VEGFA+肿瘤上皮细胞，这类细胞具备血管生成特性，且以癌基因LMO2的表达作为标记。LMO2阳性基底细胞的丰度与肿瘤内皮细胞含量呈正相关，且可预测患者较差的远处无复发生存期。我们通过构建MMTV-PyMT/Lmo2CreERT2小鼠模型，证实Lmo2谱系示踪的细胞可整合进入血管系统，且具有更高的转移倾向。在人类乳腺癌肿瘤中敲低LMO2，可通过损害肿瘤内渗过程减少肺转移，进而降低循环肿瘤细胞的出现频率。机制层面研究发现，LMO2可与STAT3结合，且是TNF-α与IL-6介导的STAT3激活所必需的。综上，本研究鉴定出一类转移起始细胞群……（简要概述）
本仓库包含两个主要文件夹：
(1) `data` 文件夹：涵盖本研究基因组分析所用的原始与处理后数据，包括本实验室的原始单细胞RNA测序（scRNA-seq）数据，以及其他实验室公开可用的scRNA-seq数据；
(2) `scripts` 文件夹：包含用于生成论文中所有图表结果的代码与脚本。若您对本文附带的数据与脚本存在任何疑问，请直接与我们联系。
所有数据均以制表符分隔的文本文件格式存储，可通过任意电子表格软件打开。所有代码均使用R或bash语言编写。