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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760
Prospective identification of tumorigenic breast cancer cells
Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530291100 · Cited by 10,370
Self-citationThe 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
Ginestier, C., Hur, M. H., Charafe-Jauffret, E., Monville, F., Dutcher, J., Brown, M., Jacquemier, J., Viens, P., Kleer, C. G., Liu, S., et al. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.08.014 · Cited by 4,012
Self-citationClarke, M. F., Dick, J. E., Dirks, P. B., Eaves, C. J., Jamieson, C. H. M., Jones, D. L., Visvader, J., Weissman, I. L., & Wahl, G. M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-3126 · Cited by 3,051
Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858 · cited 3×
“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).”
BackgroundInfluentialBerns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.030 · Cited by 1,627
Iliopoulos, D., Hirsch, H. A., & Struhl, K. (2009) · Cell · doi:10.1016/j.cell.2009.10.014 · Cited by 1,374
Iliopoulos, D., Jaeger, S. A., Hirsch, H. A., Bulyk, M. L., & Struhl, K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.07.023 · Cited by 830
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
Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells
Sullivan, N. J., Sasser, A. K., Axel, A. E., Vesuna, F., Raman, V, Ramirez, N., Oberyszyn, T. M., & Hall, B. M. (2009) · Oncogene · doi:10.1038/onc.2009.180 · Cited by 757
CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts
Ginestier, C., Liu, S., Diebel, M. E., Korkaya, H., Luo, M., Brown, M., Wicinski, J., Cabaud, O., Charafe-Jauffret, E., Birnbaum, D., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39397 · Cited by 747
Self-citationSurvival of the Fittest: Cancer Stem Cells in Therapeutic Resistance and Angiogenesis
Eyler, C. E., & Rich, J. N. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.1829 · Cited by 737
The Tumor Suppressor p53 Regulates Polarity of Self-Renewing Divisions in Mammary Stem Cells
Cicalese, A., Bonizzi, G., Pasi, C. E., Faretta, M., Ronzoni, S., Giulini, B., Brisken, C., Minucci, S., Di Fiore, P. P., & Pelicci, P. G. (2009) · Cell · doi:10.1016/j.cell.2009.06.048 · Cited by 696
Iliopoulos, D., Hirsch, H. A., Wang, G., & Struhl, K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018898108 · Cited by 643
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion
Korkaya, H., Paulson, A., Iovino, F., & Wicha, M. S. (2008) · Oncogene · doi:10.1038/onc.2008.207 · Cited by 556
Self-citationInflammation and Cancer: IL-6 and STAT3 Complete the Link
Bromberg, J., & Wang, T. C. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.009 · Cited by 542
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
Self-citationCirculating interleukin‐6 predicts survival in patients with metastatic breast cancer
Salgado, R., Junius, S., Benoy, I., Van Dam, P., Vermeulen, P., Van Marck, E., Huget, P., & Dirix, L. Y. (2003) · International Journal of Cancer · doi:10.1002/ijc.10833 · Cited by 435
Yao, Z., Fenoglio, S., Gao, D. C., Camiolo, M., Stiles, B., Lindsted, T., Schlederer, M., Johns, C., Altorki, N., Mittal, V., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009472107 · Cited by 389
Regulation of Cancer Stem Cells by Cytokine Networks: Attacking Cancer's Inflammatory Roots
Korkaya, H., Liu, S., & Wicha, M. S. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2743 · Cited by 334
Self-citationBachelot, T., Ray-Coquard, I., Menetrier-Caux, C., Rastkha, M., Duc, A., & Blay, J.-Y. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600956 · Cited by 317
Interleukin‐6 Trans‐Signalling in Chronic Inflammation and Cancer
Scheller, J., Ohnesorge, N., & Rose‐John, S. (2006) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2006.01750.x · Cited by 297
Morrison, R., Schleicher, S. M., Sun, Y., Niermann, K. J., Kim, S., Spratt, D. E., Chung, C. H., & Lu, B. (2011) · Journal of Oncology · doi:10.1155/2011/941876 · Cited by 247
IL-6 is required for glioma development in a mouse model
Weissenberger, J., Loeffler, S., Kappeler, A., Kopf, M., Lukes, A., Afanasieva, T. A., Aguzzi, A., & Weis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207455 · Cited by 189
Hartman, Z. C., Yang, X.-Y., Glass, O., Lei, G., Osada, T., Dave, S. S., Morse, M. A., Clay, T. M., & Lyerly, H. K. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0308 · Cited by 137
Yu, L., Baxter, P. A., Voicu, H., Gurusiddappa, S., Zhao, Y., Adesina, A. M., Man, T., Shu, Q., Zhang, Y.-J., Zhao, X.-M., et al. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop056 · Cited by 104
Mechanisms of Trastuzumab Resistance and Their Clinical Implications
Lan, K., Lu, C., & Yu, D. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1339.026 · Cited by 75
D'Anello, L., Sansone, P., Storci, G., Mitrugno, V., D’Uva, G., Chieco, P., & Bonafè, M. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-300 · Cited by 70
He, W., Luistro, L. L., Carvajal, D. M., Smith, M., Nevins, T., Yin, X., Cai, J. J., Higgins, B., Kolinsky, K. D., Rizzo, C., et al. (2011) · Molecular Oncology · doi:10.1016/j.molonc.2011.01.001 · Cited by 51
(2003) · PubMed
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
Su, S., Chen, J., Yao, H., Liu, J., Yu, S., Lao, L., Wang, M., Luo, M., Xing, Y., Chen, F., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.009 · Cited by 1,230
Drug Resistance Driven by Cancer Stem Cells and Their Niche
Prieto-Vila, M., Takahashi, R.-U., Usuba, W., Kohama, I., & Ochiya, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122574 · Cited by 508
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
