The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Activation of an IL6 Inflammatory Loop Mediates Trastuzumab Resistance in HER2+ Breast Cancer by Expanding the Cancer Stem Cell Population
Open accessAbstract
Although inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab, the mechanisms mediating this resistance remain elusive. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrate that development of trastuzumab resistance in these cells is mediated by activation of an IL-6 inflammatory feedback loop leading to expansion of the cancer stem cell (CSC) population. Long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL-6 than parental cells. An IL-6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies demonstrate that trastuzumab resistance may be mediated by an IL-6 inflammatory loop and suggest that blocking this loop may provide alternative strategy to overcome trastuzumab resistance.
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“MOLCE been proposed, the most common molecular alteration associated with this resistance is inactivation of the tumor suppressor PTEN, found in over 40% of HER2-positive breast cancers (Nagata et al., 2004).”
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Cited by
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
NF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679
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Drug Resistance Driven by Cancer Stem Cells and Their Niche
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The Role of Cytokines in Breast Cancer Development and Progression
Esquivel-Velázquez, M., Ostoa-Saloma, P., Palacios-Arreola, M. I., Nava-Castro, K. E., Castro, J. I., & Morales-Montor, J. (2015) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2014.0026 · Cited by 490
Metadata
- Authors
- Korkaya, H., Kim, G.-I., Davis, A., Malik, F., Henry, N. L., Ithimakin, S., Quraishi, A. A., Tawakkol, N., D'Angelo, R., Paulson, A. K., Chung, S., Luther, T., Paholak, H. J., Liu, S., Hassan, K. A., Zen, Q., Clouthier, S. G., & Wicha, M. S.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 47
- Issue
- 4
- Pages
- 570-584
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2115585914
- Cited by
- 538
- References
- 31
- FWCI
- 21.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Korkaya, H., Kim, G.-I., Davis, A., Malik, F., Henry, N. L., Ithimakin, S., Quraishi, A. A., Tawakkol, N., D'Angelo, R., Paulson, A. K., Chung, S., Luther, T., Paholak, H. J., Liu, S., Hassan, K. A., Zen, Q., Clouthier, S. G., & Wicha, M. S. (2012). Activation of an IL6 Inflammatory Loop Mediates Trastuzumab Resistance in HER2+ Breast Cancer by Expanding the Cancer Stem Cell Population. Molecular Cell. https://doi.org/10.1016/j.molcel.2012.06.014
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
