The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Selective targeting of radiation-resistant tumor-initiating cells
Open accessAbstract
Tumor-initiating cells (TICs) have been shown both experimentally and clinically to be resistant to radiation and chemotherapy, potentially resulting in residual disease that can lead to recurrence. In this study, we demonstrate that TICs isolated from p53 null mouse mammary tumors repair DNA damage following in vivo ionizing radiation more efficiently than the bulk of the tumor cells. Down-regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was observed both in fluorescence activated cell sorting (FACS)-isolated TICs as compared to non-TICs and in TIC-enriched mammospheres as compared to primary tumor cells depleted of TICs. This effect was accompanied by increased Akt signaling, as well as by the direct activation of the canonical Wnt/β-catenin signaling pathway specifically within the TIC subpopulation by phosphorylation of β-catenin on serine 552. Using limiting dilution transplantation performed on p53 null tumor cells transduced with Wnt reporter lentivirus, we demonstrated that FACS sorting of cells expressing TOP-eGFP resulted in a marked enrichment for TICs. Furthermore, FACS analysis demonstrated that cells with active Wnt signaling overlapped with the TIC subpopulation characterized previously using cell surface markers. Finally, pharmacological inhibition of the Akt pathway in both mammospheres and syngeneic mice bearing tumors was shown to inhibit canonical Wnt signaling as well as the repair of DNA damage selectively in TICs, sensitizing them to ionizing radiation treatment. Thus, these results suggest that pretreatment with Akt inhibitors before ionizing radiation treatment may be of potential therapeutic benefit to patients.
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Cites
Association of reactive oxygen species levels and radioresistance in cancer stem cells
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A role for Wnt signalling in self-renewal of haematopoietic stem cells
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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
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“Loss of PTEN, and thus the activation of the PI3K/ Akt signaling pathway, contributes to chemoresistance in lung (9) and breast cancer (10).”
BackgroundPTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
Zhang, J., Grindley, J. C., Yin, T., Jayasinghe, S., He, X. C., Ross, J. T., Haug, J. S., Rupp, D., Porter-Westpfahl, K. S., Wiedemann, L. M., et al. (2006) · Nature · doi:10.1038/nature04747 · Cited by 817
Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling
Korkaya, H., Paulson, A., Charafe-Jauffret, E., Ginestier, C., Brown, M., Dutcher, J., Clouthier, S. G., & Wicha, M. S. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000121 · Cited by 523
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“Loss of PTEN, and thus the activation of the PI3K/ Akt signaling pathway, contributes to chemoresistance in lung (9) and breast cancer (10).”
BackgroundPTEN negatively regulates neural stem cell self-renewal by modulating G 0 -G 1 cell cycle entry
Groszer, M., Erickson, R., Scripture-Adams, D. D., Dougherty, J. D., Le Belle, J., Zack, J. A., Geschwind, D. H., Liu, X., Kornblum, H. I., & Wu, H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509939103 · Cited by 306
Cited by
The DNA damage response and cancer therapy
Lord, C. J., & Ashworth, A. (2012) · Nature · doi:10.1038/nature10760 · Cited by 1,649
Cancer Stem Cells: Current Status and Evolving Complexities
Visvader, J. E., & Lindeman, G. J. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.007 · Cited by 1,287
Wang, S., Li, X., Chen, Y., Cai, X., Yao, H., Gao, W., Zheng, Y., An, X., Shi, J., & Chen, H. (2015) · Advanced Materials · doi:10.1002/adma.201500870 · Cited by 438
Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review
Singh, N., Miner, A., Hennis, L., & Mittal, S. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.79 · Cited by 398
Vitale, I., Manic, G., De Maria, R., Kroemer, G., & Galluzzi, L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.006 · Cited by 361
Metadata
- Authors
- Zhang, M., Atkinson, R. L., & Rosen, J. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-02-23
- Volume
- 107
- Issue
- 8
- Pages
- 3522-3527
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2049589513
- Cited by
- 216
- References
- 8
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- green
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