The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
p66Shc/Notch-3 Interplay Controls Self-Renewal and Hypoxia Survival in Human Stem/Progenitor Cells of the Mammary Gland Expanded In Vitro as Mammospheres
Abstract
The comprehension of the basic biology of stem cells is expected to provide a useful insight into the pathogenesis of cancer. In particular, there is evidence that hypoxia promotes stem cell renewal in vitro as well as in vivo. It therefore seems reasonable that stem cell survival and hypoxia response are strictly connected at molecular level. We here report that the 66-kDa isoform of the SHC gene (p66Shc) is induced in a breast cancer cell line by the exposure to hypoxic environment and that it controls the expression of the stem cell regulatory gene Notch-3. Then, we show that p66Shc/Notch-3 interplay modulates self-renewal (by inducing the Notch-ligand Jagged-1) and hypoxia survival (by inducing the hypoxia-survival gene carbonic anhydrase IX) in mammary gland stem/progenitor cells, expanded in vitro as multicellular spheroids (mammospheres). We conclude that mechanisms that regulate stem cell renewal and hypoxia survival are integrated at the level of the p66Shc/Notch3 interplay. Because Notch-3, Jagged-1, and carbonic anhydrase IX are dysregulated in breast cancer, and because p66Shc is an aging-regulating gene, we envision that these data may help in understanding the relationship among aging, cancer, and stem cells.
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Cites
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Pleiotropy, natural selection, and the evolution of senescence
Williams, G. C. (1957) · Evolution · doi:10.2307/2406060 · Cited by 1,912
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712
Cancer stem cells: an old idea–a paradigm shift
Wicha, M. S., Liu, S., & Dontu, G. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3153 · Cited by 1,378
Hypoxia requires Notch signaling to maintain the undifferentiated cell state
Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U., & Bondesson, M. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.010 · Cited by 1,109
Cited by
Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells
Gupta, P. B., Fillmore, C. M., Jiang, G., Shapira, S. D., Tao, K., Kuperwasser, C., & Lander, E. S. (2011) · Cell · doi:10.1016/j.cell.2011.07.026 · Cited by 1,475
Sansone, P., Storci, G., Tavolari, S., Guarnieri, T., Giovannini, C., Taffurelli, M., Ceccarelli, C., Santini, D., Paterini, P., Marcu, K. B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32533 · Cited by 779
Self-citationHypoxia or in situ normoxia: The stem cell paradigm
Ivanovic, Z. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21690 · Cited by 406
Metadata
- Authors
- Sansone, P., Storci, G., Giovannini, C., Pandolfi, S., Pianetti, S., Taffurelli, M., Santini, D., Ceccarelli, C., Chieco, P., & Bonafé, M.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-07
- Volume
- 25
- Issue
- 3
- Pages
- 807-815
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2048838448
- Cited by
- 190
- References
- 5
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- closed
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