The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells
Open accessAbstract
Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated by stem-like cells that proliferate and differentiate to produce advanced metastatic disease.
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Cites
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M., Reinhard, F., Zhang, C. C., Shipitsin, M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.027 · Cited by 8,672
Self-citationTriple-negative breast cancer: clinical features and patterns of recurrence
Dent, R., Trudeau, M., Pritchard, K. I., Hanna, W. M., Kahn, H. K., Sawka, C. A., Lickley, L. A., Rawlinson, E., Sun, P., & Narod, S. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3045 · Cited by 5,091
Györffy, B., Lanczky, A., Eklund, A. C., Denkert, C., Budczies, J., Li, Q., & Szallasi, Z. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0674-9 · Cited by 4,169
Hermann, P. C., Huber, S. L., Herrler, T., Aicher, A., Ellwart, J. W., Guba, M., Bruns, C. J., & Heeschen, C. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.06.002 · Cited by 2,897
Breast cancer metastasis: markers and models
Weigelt, B., Peterse, J. L., & van't Veer, L. J. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1670 · Cited by 2,232
Generation of a functional mammary gland from a single stem cell
Shackleton, M., Vaillant, F., Simpson, K. J., Stingl, J., Smyth, G. K., Asselin-Labat, M.-L., Wu, L., Lindeman, G. J., & Visvader, J. E. (2006) · Nature · doi:10.1038/nature04372 · Cited by 2,005
Purification and unique properties of mammary epithelial stem cells
Stingl, J., Eirew, P., Ricketson, I., Shackleton, M., Vaillant, F., Choi, D., Li, H. I., & Eaves, C. J. (2006) · Nature · doi:10.1038/nature04496 · Cited by 1,559
kConFab, Lim, E., Vaillant, F., Wu, D., Forrest, N. C., Pal, B., Hart, A. H., Asselin-Labat, M.-L., Gyorki, D. E., Ward, T., et al. (2009) · Nature Medicine · doi:10.1038/nm.2000 · Cited by 1,492
DeRose, Y. S., Wang, G., Lin, Y.-C., Bernard, P. S., Buys, S. S., Ebbert, M. T. W., Factor, R., Matsen, C., Milash, B. A., Nelson, E., et al. (2011) · Nature Medicine · doi:10.1038/nm.2454 · Cited by 1,002
Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State
Guo, W., Keckesova, Z., Donaher, J. L., Shibue, T., Tischler, V., Reinhardt, F., Itzkovitz, S., Noske, A., Zürrer-Härdi, U., Bell, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.008 · Cited by 957
Cited by
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062
Steeg, P. S. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.25 · Cited by 1,363
Peng, J., Sun, B.-F., Chen, C.-Y., Zhou, J.-Y., Chen, Y.-S., Chen, H., Liu, L., Huang, D., Jiang, J., Cui, G.-S., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0195-y · Cited by 1,321
Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer
Chung, W., Eum, H. H., Lee, H.-O., Lee, K.-M., Lee, H.-B., Kim, K.-T., Ryu, H. S., Kim, S., Lee, J. E., Park, Y. H., et al. (2017) · Nature Communications · doi:10.1038/ncomms15081 · Cited by 992
“Carcinoma cells variably expressed aggressive cancer signatures such as epithelial–mesenchymal transition (EMT), stemness, angiogenesis, proliferation 29,30 and recurrence 3,31 (Supplementary Fig.”
Metadata
- Authors
- Lawson, D. A., Bhakta, N. R., Kessenbrock, K., Prummel, K. D., Yu, Y., Takai, K., Zhou, A., Eyob, H., Balakrishnan, S., Wang, C.-Y., Yaswen, P., Goga, A., & Werb, Z.
- Venue
- Nature
- Published
- 2015-09-23
- Volume
- 526
- Issue
- 7571
- Pages
- 131-135
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1835915349
- Cited by
- 893
- References
- 32
- FWCI
- 36.92
- Type
- journal article
- Language
- en
- Open access
- green
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- Lawson, D. A., Bhakta, N. R., Kessenbrock, K., Prummel, K. D., Yu, Y., Takai, K., Zhou, A., Eyob, H., Balakrishnan, S., Wang, C.-Y., Yaswen, P., Goga, A., & Werb, Z. (2015). Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. https://doi.org/10.1038/nature15260
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