The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments
Open accessAbstract
Hypoxia is a poor-prognosis microenvironmental hallmark of solid tumours, but it is unclear how it influences the fate of disseminated tumour cells (DTCs) in target organs. Here we report that hypoxic HNSCC and breast primary tumour microenvironments displayed upregulation of key dormancy (NR2F1, DEC2, p27) and hypoxia (GLUT1, HIF1α) genes. Analysis of solitary DTCs in PDX and transgenic mice revealed that post-hypoxic DTCs were frequently NR2F1hi/DEC2hi/p27hi/TGFβ2hi and dormant. NR2F1 and HIF1α were required for p27 induction in post-hypoxic dormant DTCs, but these DTCs did not display GLUT1hi expression. Post-hypoxic DTCs evaded chemotherapy and, unlike ER− breast cancer cells, post-hypoxic ER+ breast cancer cells were more prone to enter NR2F1-dependent dormancy. We propose that primary tumour hypoxic microenvironments give rise to a subpopulation of dormant DTCs that evade therapy. These post-hypoxic dormant DTCs may be the source of disease relapse and poor prognosis associated with hypoxia.
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2 retracted
Lysyl oxidase is essential for hypoxia-induced metastasis
Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.-T., Chi, J.-T. A., Jeffrey, S. S., & Giaccia, A. J. (2006) · Nature · doi:10.1038/nature04695 · Cited by 1,309
RetractedGilkes, D. M., Bajpai, S., Chaturvedi, P., Wirtz, D., & Semenza, G. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442939 · Cited by 467
RetractedTargeting hypoxia in cancer therapy
Wilson, W. R., & Hay, M. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3064 · Cited by 3,172
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.027 · Cited by 2,770
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520
Mechanisms of disseminated cancer cell dormancy: an awakening field
Sosa, M. S., Bragado, P., & Aguirre-Ghiso, J. A. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3793 · Cited by 1,126
Self-citationHypoxia signalling through mTOR and the unfolded protein response in cancer
Wouters, B. G., & Koritzinsky, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2501 · Cited by 894
ER stress‐regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
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Long-term human breast carcinoma cell lines of metastatic origin: Preliminary characterization
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Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells
Keller, L., & Pantel, K. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0180-2 · Cited by 544
Systems Biology of Cancer Metastasis
Suhail, Y., Cain, M. P., Vanaja, K., Kurywchak, P. A., Levchenko, A., Kalluri, R., & Kshitiz (2019) · Cell Systems · doi:10.1016/j.cels.2019.07.003 · Cited by 452
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities
Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210
Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2
Nobre, A. R., Risson, E., Singh, D. K., Di Martino, J. S., Cheung, J. F., Wang, J., Johnson, J., Russnes, H. G., Bravo-Cordero, J. J., Birbrair, A., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00179-8 · Cited by 159
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Metadata
- Authors
- Fluegen, G., Avivar-Valderas, A., Wang, Y., Padgen, M. R., Williams, J. K., Nobre, A. R., Calvo, V., Cheung, J. F., Bravo-Cordero, J. J., Entenberg, D., Castracane, J., Verkhusha, V., Keely, P. J., Condeelis, J., & Aguirre-Ghiso, J. A.
- Venue
- Nature Cell Biology
- Published
- 2017-01-23
- Volume
- 19
- Issue
- 2
- Pages
- 120-132
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2580755748
- Cited by
- 336
- References
- 58
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- green
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- Fluegen, G., Avivar-Valderas, A., Wang, Y., Padgen, M. R., Williams, J. K., Nobre, A. R., Calvo, V., Cheung, J. F., Bravo-Cordero, J. J., Entenberg, D., Castracane, J., Verkhusha, V., Keely, P. J., Condeelis, J., & Aguirre-Ghiso, J. A. (2017). Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nature Cell Biology. https://doi.org/10.1038/ncb3465
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