Combined Single-Cell and Spatial Transcriptomics Reveal the Metabolic Evolvement of Breast Cancer during Early Dissemination.
IF: 17.521


Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA-seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis.


Spatial Transcriptomics
breast cancer
early dissemination
single-cell RNA sequencing
spatial transcriptomics

MeSH terms

Breast Neoplasms
Lymphatic Metastasis
Lymph Nodes


Liu, Yi-Ming
Ge, Jing-Yu
Chen, Yu-Fei
Liu, Tong
Chen, Lie
Liu, Cui-Cui
Ma, Ding
Chen, Yi-Yu
Cai, Yu-Wen
Xu, Ying-Ying
Shao, Zhi-Ming
Yu, Ke-Da