ArticleProceedings of the National Academy of Sciences of the United States of America2019
Energetic regulation of coordinated leader-follower dynamics during collective invasion of breast cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed.
- CCL5 and GLUT1 define leader cells in collective invasion of colorectal cancer.The Journal of pathology · 2026Article
- Invasion dynamics of multifocal breast tumor spheroids in three-dimensional extracellular matrix.Biophysical journal · 2026Article
- S100A4 promotes collective invasion of pancreatic ductal adenocarcinoma and its blockade suppresses metastasis.Cell communication and signaling : CCS · 2026Article
- EMT and cell cycle control invadopodia and metastasis in breast cancer via Filip1L.Research square · 2026Article
- Leader cell myosin 10 controls adhesion dynamics, invasion, and EMT pathway activation.Cell communication and signaling : CCS · 2026Article
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- The Interplay Between Stiffness and Hyperglycemia on Diabetic Foot Ulcer Wound Closure.Cellular and molecular bioengineering · 2026Article
- Associations of Type 2 Diabetes with Tumor Budding and Microvascular Invasion in Resected Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Metabolic programming defines oxygen-sensitive subpopulation hierarchies and patterning in collective invasion.Molecular biology of the cell · 2025Article
- Orchestrating movement: the role of Caveolin-1 in migration and metastasis.Molecular cancer · 2025Review
- Aquaporin 5 expression regulates MDA-MB-231 spheroid multicellular invasion.American journal of physiology. Cell physiology · 2025Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- Energy stress and adaptation strategy of tumor cells in different microenvironments: from primary tumors to distant metastases.Acta biochimica et biophysica Sinica · 2025Review
- Navigating confinement: Mechanotransduction and metabolic adaptation.Current opinion in cell biology · 2025Review
- Spatial regulation of mitochondrial membrane potential by α5β1 integrin engagement in collective cell migration.Journal of cell science · 2025Article
- Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.Developmental cell · 2025Article
- Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches.Journal of translational medicine · 2025Review
- TGF-β1-mediated intercellular signaling fuels cooperative cellular invasion.Cell reports · 2025Article
- Confinement, Jamming, and Adhesion in Cancer Cells Dissociating from a Collectively Invading Strand.PRX life · 2025Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
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Abstract
The ability of primary tumor cells to invade into adjacent tissues, followed by the formation of local or distant metastasis, is a lethal hallmark of cancer. Recently, locomoting clusters of tumor cells have been identified in numerous cancers and associated with increased invasiveness and metastatic potential. However, how the collective behaviors of cancer cells are coordinated and their contribution to cancer invasion remain unclear. Here we show that collective invasion of breast cancer cells is regulated by the energetic statuses of leader and follower cells. Using a combination of in vitro spheroid and ex vivo organoid invasion models, we found that cancer cells dynamically rearrange leader and follower positions during collective invasion. Cancer cells invade cooperatively in denser collagen matrices by accelerating leader-follower switching thus decreasing leader cell lifetime. Leader cells exhibit higher glucose uptake than follower cells. Moreover, their energy levels, as revealed by the intracellular ATP/ADP ratio, must exceed a threshold to invade. Forward invasion of the leader cell gradually depletes its available energy, eventually leading to leader-follower transition. Our computational model based on intracellular energy homeostasis successfully recapitulated the dependence of leader cell lifetime on collagen density. Experiments further supported model predictions that decreasing the cellular energy level by glucose starvation decreases leader cell lifetime whereas increasing the cellular energy level by AMP-activated kinase (AMPK) activation does the opposite. These findings highlight coordinated invasion and its metabolic regulation as potential therapeutic targets of cancer.
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