HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis
Open accessPublished version of a preprint
Abstract
HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells. Wild-type HER2 elicited a profound transcriptional inflammatory profile, including marked elevation of interleukin-6 (IL-6) expression, which we established to be a critical determinant of HER2 oncogenesis. Mechanistic investigations revealed that IL-6 secretion induced by HER2 overexpression activated Stat3 and altered gene expression, enforcing an autocrine loop of IL-6/Stat3 expression. Both mouse and human in vivo models of HER2-amplified breast carcinoma relied critically on this HER2–IL-6–Stat3 signaling pathway. Our studies offer the first direct evidence linking HER2 to a systemic inflammatory mechanism that orchestrates HER2-mediated tumor growth. We suggest that the HER2–IL-6–STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers. Cancer Res; 71(13); 4380–91. ©2011 AACR.
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
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HER2 expression in breast cancer activates an IL-6 autocrine signaling loop to activate STAT3, which is critical for tumorigenesis.
“Its expression in breast cancer activates an IL-6 autocrine signaling loop to activate STAT3, which is critical for tumorigenesis (321).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [321]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Matrix Metalloproteinases: Regulators of the Tumor Microenvironment
Kessenbrock, K., Plaks, V., & Werb, Z. (2010) · Cell · doi:10.1016/j.cell.2010.03.015 · Cited by 5,151 · see citing works
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383 · see citing works
Huang, D. W., Sherman, B. T., Tan, Q., Kir, J., Liu, D., Bryant, D., Guo, Y., Stephens, R. M., Baseler, M., Lane, H. C., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm415 · Cited by 2,216 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M. (2007) · Science · doi:10.1126/science.1140485 · Cited by 1,955 · see citing works
Park, E. J., Lee, J. H., Yu, G.-Y., He, G., Ali, S. R., Holzer, R. G., Österreicher, C. H., Takahashi, H., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2009.12.052 · Cited by 1,764 · see citing works
Iliopoulos, D., Hirsch, H. A., & Struhl, K. (2009) · Cell · doi:10.1016/j.cell.2009.10.014 · Cited by 1,374 · see citing works
Herschkowitz, J. I., Simin, K. J., Weigman, V., Mikaelian, I., Usary, J., Hu, Z., Rasmussen, K., Jones, L. P., Assefnia, S., Chandrasekharan, S., et al. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r76 · Cited by 1,277 · see citing works
Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis
Sparmann, A., & Bar‐Sagi, D. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.028 · Cited by 854 · see citing works
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 · see citing works
Breast cancer: origins and evolution
Polyák, K. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33295 · Cited by 703 · see citing works
Gao, S. P., Mark, K. G., Leslie, K., Pao, W., Motoi, N., Gerald, W. L., Travis, W. D., Bornmann, W., Veach, D., Clarkson, B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31871 · Cited by 666 · see citing works
Soucek, L., Lawlor, E. R., Soto, D., Shchors, K., Swigart, L. B., & Evan, G. I. (2007) · Nature Medicine · doi:10.1038/nm1649 · Cited by 508 · see citing works
Inflammation and oncogenesis: a vicious connection
Grivennikov, S. I., & Karin, M. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.11.004 · Cited by 460 · see citing works
β4 Integrin Amplifies ErbB2 Signaling to Promote Mammary Tumorigenesis
Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., & Giancotti, F. G. (2006) · Cell · doi:10.1016/j.cell.2006.05.047 · Cited by 455 · see citing works
Circulating interleukin‐6 predicts survival in patients with metastatic breast cancer
Salgado, R., Junius, S., Benoy, I. H., van Dam, P. A., Vermeulen, P., Marck, E. V., Huget, P., & Dirix, L. Y. (2002) · International Journal of Cancer · doi:10.1002/ijc.10833 · Cited by 435 · see citing works
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
Ancrile, B., Lim, K.-H., & Counter, C. M. (2007) · Genes & Development · doi:10.1101/gad.1549407 · Cited by 422 · see citing works
Significance of interleukin-6 (IL-6) in breast cancer (review)
Knüpfer, H., & Preiß, R. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9328-3 · Cited by 397 · see citing works
Autocrine IL-6 signaling: a key event in tumorigenesis?
Grivennikov, S., & Karin, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2007.12.020 · Cited by 379 · see citing works
Benoy, I. H., Salgado, R., van Dam, P. A., Geboers, K., Marck, E. V., Scharpé, S., Vermeulen, P. B., & Dirix, L. Y. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0812 · Cited by 356 · see citing works
Bachelot, T., Ray-Coquard, I., Ménétrier‐Caux, C., Rastkha, M., Duc, A., & Blay, J. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600956 · Cited by 317 · see citing works
Zhang, G.-J., & Adachi, I. (1999) · PubMed · Cited by 308 · see citing works
Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2
Wang, S., Lien, H., Xia, W., Chen, I.-F., Lo, H., Wang, Z., Ali‐Seyed, M., Lee, D., Bartholomeusz, G. A., Ou‐Yang, F., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.012 · Cited by 306 · see citing works
Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells
Qiu, Y., Ravi, L., & Kung, H.-J. (1998) · Nature · doi:10.1038/30012 · Cited by 280 · see citing works
Nicolini, A., Carpi, A., & Rossi, G. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.07.002 · Cited by 280 · see citing works
Review: IL-6 Transsignaling: The In Vivo Consequences
Jones, S. A., Richards, P. J., Scheller, J., & Rose‐John, S. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.241 · Cited by 251 · see citing works
Kozłowski, L., Zakrzewska, I., Tokajuk, P., & Wojtukiewicz, M. Z. (2003) · PubMed · Cited by 248 · see citing works
Diaz, N., Minton, S. E., Cox, C., Bowman, T. L., Gritsko, T., Garcia, R., Eweis, I., Wloch, M., Livingston, S., Seijo, E., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1749 · Cited by 241 · see citing works
Berishaj, M., Gao, S. P., Ahmed, S. T., Leslie, K., Al‐Ahmadie, H. A., Gerald, W. L., Bornmann, W. G., & Bromberg, J. (2007) · Breast Cancer Research · doi:10.1186/bcr1680 · Cited by 236 · see citing works
Patterns of microRNA expression characterize stages of human B-cell differentiation
Zhang, J., Jima, D. D., Jacobs, C. L., Fischer, R. T., Gottwein, E., Huang, G., Lugar, P., Lagoo, A. S., Rizzieri, D. A., Friedman, D. R., et al. (2009) · Blood · doi:10.1182/blood-2008-09-178186 · Cited by 226 · see citing works
Kurebayashi, J., Otsuki, T., Tang, C., Kurosumi, M., Yamamoto, S., Tanaka, K., Mochizuki, M., Nakamura, H., & Soono, H. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690114 · Cited by 196 · see citing works
Serum Interleukin 6, Plasma VEGF, Serum VEGF, and VEGF Platelet Load in Breast Cancer Patients
Benoy, I. H., Salgado, R., Colpaert, C., Weytjens, R., Vermeulen, P., & Dirix, L. Y. (2002) · Clinical Breast Cancer · doi:10.3816/cbc.2002.n.008 · Cited by 188 · see citing works
Staaf, J., Ringnér, M., Vallon‐Christersson, J., Jönsson, G. B., Bendahl, P., Holm, K., Arason, A., Gunnarsson, H., Hegardt, C., Agnarsson, B. A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.8775 · Cited by 173 · see citing works
Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes
Brugarolas, J., & Kaelin, W. G. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.020 · Cited by 162 · see citing works
Identification of Novel Kinase Targets for the Treatment of Estrogen Receptor–Negative Breast Cancer
Speers, C. W., Tsimelzon, A. I., Sexton, K. R., Herrick, A. M., Gutiérrez, C., Culhane, A. C., Quackenbush, J. F., Hilsenbeck, S. G., Chang, J. C., & Brown, P. H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1107 · Cited by 110 · see citing works
Bozcuk, H. S., Uslu, G., Samur, M., Yıldız, M., Özben, T., Özdoğan, M., Artaç, M., Altunbaş, H., Akan, I., & Savaş, B. (2004) · Cytokine · doi:10.1016/j.cyto.2004.04.002 · Cited by 106 · see citing works
Gene-Engineered T Cells as a Superior Adjuvant Therapy for Metastatic Cancer
Kershaw, M. H., Jackson, J. T., Haynes, N. M., Teng, M. W. L., Moeller, M., Hayakawa, Y., Street, S. E. A., Cameron, R., Tanner, J. E., Trapani, J. A., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.2143 · Cited by 84 · see citing works
Grant, S. L., Hammacher, A., Douglas, A. M., Goss, G. A., Mansfield, R., Heath, J. K., & Begley, C. G. (2002) · Oncogene · doi:10.1038/sj.onc.1205100 · Cited by 63 · see citing works
Landis, M. D., Seachrist, D. D., Montanez-Wiscovich, M. E., Danielpour, D., & Keri, R. A. (2005) · Oncogene · doi:10.1038/sj.onc.1208712 · Cited by 58 · see citing works
Hartman, Z. C., Wei, J.-P., Osada, T., Glass, O., Lei, G., Yang, X.-Y., Peplinski, S., Kim, D., Xia, W., Spector, N. L., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2549 · Cited by 30 · see citing works
Self-citation
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“Its expression in breast cancer activates an IL-6 autocrine signaling loop to activate STAT3, which is critical for tumorigenesis (321).”
BackgroundInterleukin-6 signaling pathway in targeted therapy for cancer.
Guo, Y.-Q., Xu, F., Lu, T. J., Duan, Z., & Zhang, Z. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.04.007 · Cited by 690 · see citing works
Constitutive activation of <scp>STAT</scp>3 in breast cancer cells: A review
Banerjee, K., & Resat, H. (2016) · International Journal of Cancer · doi:10.1002/ijc.29923 · Cited by 611 · see citing works
Korkaya, H., Kim, G., Davis, A., Malik, F., Henry, N., Ithimakin, S., Quraishi, A. A., Tawakkol, N., D'Angelo, R., Paulson, A. K., et al. (2012) · Molecules and Cells · doi:10.1016/j.molcel.2012.06.014 · Cited by 518 · see citing works
Cancer and Inflammation: An Old Intuition with Rapidly Evolving New Concepts
Trinchieri, G. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075008 · Cited by 506 · see citing works
The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis
Chang, Q., Bournazou, E., Sansone, P., Berishaj, M., Gao, S. P., Daly, L., Wels, J., Theilen, T., Granitto, S., Zhang, X., et al. (2013) · Neoplasia · doi:10.1593/neo.13706 · Cited by 494 · see citing works
Hartman, Z. C., Poage, G. M., den Hollander, P., Tsimelzon, A. I., Hill, J. L., Panupinthu, N., Zhang, Y., Mazumdar, A., Hilsenbeck, S. G., Mills, G. B., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4524-t · Cited by 408 · see citing works
Self-citationIbrahim, S., Gadalla, R., Elghonaimy, E. A., Samir, O., Mohamed, H. T., Hassan, H., Greve, B., El‐Shinawi, M., Mohamed, M. M., & Götte, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0621-z · Cited by 273 · see citing works
Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells
Singh, J. K., Simões, B. M., Howell, S. J., Farnie, G., & Clarke, R. B. (2013) · Breast Cancer Research · doi:10.1186/bcr3436 · Cited by 250 · see citing works
López de Andrés, J., Griñán-Lisón, C., Jiménez, G., & Marchal, J. A. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00966-3 · Cited by 207 · see citing works
Gao, Q., Zhao, Y., Wang, X., Qiu, S., Shi, Y., Sun, J. H., Yi, Y., Shi, J.-Y., Shi, G., Ding, Z., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-4032 · Cited by 174 · see citing works
CHUNG, S. S., Giehl, N. M., Wu, Y., & Vadgama, J. V. (2013) · International Journal of Oncology · doi:10.3892/ijo.2013.2195 · Cited by 161 · see citing works
Mattos‐Arruda, L. D., Bottai, G., Nuciforo, P. G., Tommaso, L. D., Giovannetti, E., Peg, V., Losurdo, A., Pérez-García, J. M., Masci, G., Corsi, F., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5495 · Cited by 156 · see citing works
Tumor target amplification: Implications for nano drug delivery systems
Seidi, K., Neubauer, H. A., Moriggl, R., Jahanban-Esfahlan, R., & Javaheri, T. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.02.020 · Cited by 145 · see citing works
Witek Janusek, L., Tell, D., & Mathews, H. L. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.04.012 · Cited by 143 · see citing works
Garg, M., Shanmugam, M. K., Bhardwaj, V., Goel, A., Gupta, R., Sharma, A., Baligar, P., Kumar, A. P., Goh, B. C., Wang, L., et al. (2020) · Medicinal Research Reviews · doi:10.1002/med.21761 · Cited by 142 · see citing works
Streicher, K. L., Zhu, W., Lehmann, K. P., Georgantas, R. W., Morehouse, C. A., Brohawn, P. Z., Carrasco, R. A., Xiao, Z., Tice, D., Higgs, B. W., et al. (2011) · Oncogene · doi:10.1038/onc.2011.345 · Cited by 136 · see citing works
Eiring, A. M., Page, B. D. G., Kraft, I. L., Mason, C. C., Vellore, N. A., Resetca, D., Zabriskie, M. S., Zhang, T. Y., Khorashad, J. S., Engar, A., et al. (2014) · Leukemia · doi:10.1038/leu.2014.245 · Cited by 132 · see citing works
PI3K and STAT3: A New Alliance
Vogt, P. K., & Hart, J. R. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0218 · Cited by 128 · see citing works
Is Red Cell Distribution Width a Novel Biomarker of Breast Cancer Activity? Data From a Pilot Study
Seretis (2013) · Journal of Clinical Medicine Research · doi:10.4021/jocmr1214w · Cited by 126 · see citing works
Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer
Heo, T., Wahler, J., & Suh, N. (2016) · Oncotarget · doi:10.18632/oncotarget.7102 · Cited by 122 · see citing works
Alberti, C., Pinciroli, P., Valeri, B., Ferri, R., Ditto, A., Umezawa, K., Sensi, M., Canevari, S., & Tomassetti, A. (2011) · Oncogene · doi:10.1038/onc.2011.572 · Cited by 115 · see citing works
Barrueco, R. R., Yu, J., Saucedo-Cuevas, L. P., Oliván, M., Llobet‐Navàs, D., Putcha, P., Castro, V., Murga-Penas, E., Collazo-Lorduy, A., Castillo-Martín, M., et al. (2015) · Genes & Development · doi:10.1101/gad.262642.115 · Cited by 108 · see citing works
Kim, M. S., Lee, W. S., Jeong, J., Kim, S., & Jin, W. (2015) · Oncotarget · doi:10.18632/oncotarget.5522 · Cited by 109 · see citing works
CHUNG, S. S., Aroh, C., & Vadgama, J. V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083971 · Cited by 104 · see citing works
Khan, M. W., Saadalla, A., Ewida, A. H., Al-Katranji, K., Al-Saoudi, G., Giaccone, Z. T., Gounari, F., Zhang, M., Frank, D. A., & Khazaie, K. (2018) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-017-2057-0 · Cited by 103 · see citing works
The IL-6 feed-forward loop: A driver of tumorigenesis
Chang, Q., Daly, L., & Bromberg, J. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.01.007 · Cited by 99 · see citing works
Liu, S., Lee, J. S., Jie, C., Park, M. H., Iwakura, Y., Patel, Y. K., Soni, M., Reisman, D., & Chen, H. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2761 · Cited by 95 · see citing works
Inflamm‐aging of the stem cell niche: Breast cancer as a paradigmatic example
Bonafè, M., Storci, G., & Franceschi, C. (2011) · BioEssays · doi:10.1002/bies.201100104 · Cited by 93 · see citing works
Menghini, L., Ferrante, C., Leporini, L., Recinella, L., Chiavaroli, A., Leone, S., Pintore, G., Vacca, M., Orlando, G., & Brunetti, L. (2016) · Phytotherapy Research · doi:10.1002/ptr.5655 · Cited by 90 · see citing works
Jiang, L., Ren, L., Chen, H., Pan, J., Zhang, Z., Kuang, X., Chen, X., Bao, W., Lin, C., Zhou, Z., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02753-x · Cited by 80 · see citing works
Bcl3 Selectively Promotes Metastasis of ERBB2-Driven Mammary Tumors
Wakefield, A., Soukupová, J., Montagne, A., Ranger, J. J., French, R., Muller, W. J., & Clarkson, R. W. E. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1321 · Cited by 77 · see citing works
Mazzarella, L., Disalvatore, D., Bagnardi, V., Rotmensz, N., Galbiati, D., Caputo, S., Curigliano, G., & Pelicci, P. G. (2013) · European Journal of Cancer · doi:10.1016/j.ejca.2013.07.016 · Cited by 76 · see citing works
HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance
Nami, B., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050040 · Cited by 75 · see citing works
Vivekanandhan, S., & Knutson, K. L. (2022) · Cancers · doi:10.3390/cancers14205115 · Cited by 76 · see citing works
Luo, F., Xu, Y., Ling, M., Zhao, Y., Xu, W., Xiao, L., Jiang, R., Wang, B., Bian, Q., & Liu, Q. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.08.025 · Cited by 73 · see citing works
Locatelli, M., Macchione, N., Ferrante, C., Chiavaroli, A., Recinella, L., Carradori, S., Zengin, G., Cesa, S., Leporini, L., Leone, S., et al. (2018) · Molecules · doi:10.3390/molecules23051145 · Cited by 71 · see citing works
Thirkettle, S., Decock, J. V., Arnold, H., Pennington, C. J., Jaworski, D. M., & Edwards, D. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.464230 · Cited by 70 · see citing works
Xiang, S., Dauchy, R. T., Hoffman, A. E., Pointer, D. T., Frasch, T., Blask, D. E., & Hill, S. M. (2019) · Journal of Pineal Research · doi:10.1111/jpi.12586 · Cited by 70 · see citing works
Cellular Plasticity in Breast Cancer Progression and Therapy
Kong, D., Hughes, C. J., & Ford, H. L. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00072 · Cited by 67 · see citing works
The Role of Inflammation in Inflammatory Breast Cancer
Fouad, T. M., Kogawa, T., Reuben, J. M., & Ueno, N. T. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_3 · Cited by 67 · see citing works
STAT1 gene expression is enhanced by nuclear EGFR and HER2 via cooperation With STAT3
Han, W., Carpenter, R. L., Cao, X., & Lo, H. (2012) · Molecular Carcinogenesis · doi:10.1002/mc.21936 · Cited by 66 · see citing works
Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration
Buchheit, C. L., Angarola, B. L., Steiner, A., Weigel, K. J., & Schafer, Z. T. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.209 · Cited by 63 · see citing works
Ray, K., Újvári, B., Ramana, V., & Donald, J. A. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.04.002 · Cited by 62 · see citing works
Aghazadeh, S., & Yazdanparast, R. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.05.009 · Cited by 63 · see citing works
Targeting of Rac GTPases blocks the spread of intact human breast cancer
Katz, E., Sims, A. H., Sproul, D., Caldwell, H., Dixon, J. M., Meehan, R. R., & Harrison, D. J. (2012) · Oncotarget · doi:10.18632/oncotarget.520 · Cited by 62 · see citing works
Janusek, L. W., Tell, D., Albuquerque, K., & Mathews, H. L. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.05.014 · Cited by 63 · see citing works
lnflammation-induced epigenetic switches in cancer
Rokavec, M., Öner, M. G., & Hermeking, H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2045-5 · Cited by 61 · see citing works
Multifaceted functions of chronic inflammation in regulating tumor dormancy and relapse
Manjili, S. H., Isbell, M., Ghochaghi, N., Perkinson, T., & Manjili, M. H. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.023 · Cited by 59 · see citing works
Bamodu, O. A., Huang, W.-C., Tzeng, D. T. W., Wu, A. T. H., Wang, L. S., Yeh, C., & Chao, T.-Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.05.006 · Cited by 56 · see citing works
Koellensperger, E., Bonnert, L.-C., Zoernig, I., Marmé, F., Sandmann, S., Germann, G., Gramley, F., & Leimer, U. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0579-1 · Cited by 56 · see citing works
Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer
Tschui, J., Vassella, E., Bandi, N., Baumgartner, U., Genitsch, V., Rotzer, D., Seiler, R., Thalmann, G. N., & Fleischmann, A. (2015) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-015-1729-4 · Cited by 55 · see citing works
Elevated PI3K signaling drives multiple Breast Cancer subtypes
Adams, J. R., Schachter, N. F., Liu, J. C., Zacksenhaus, E., & Egan, S. E. (2011) · Oncotarget · doi:10.18632/oncotarget.285 · Cited by 52 · see citing works
Jeon, M., You, D., Bae, S. Y., Kim, S. W., Nam, S. J., Kim, H. H., Kim, S., & Lee, J. E. (2016) · Oncotarget · doi:10.18632/oncotarget.10843 · Cited by 52 · see citing works
Gene Expression Meta-Analysis of Potential Metastatic Breast Cancer Markers
Bell, R., Barraclough, R., & Vasieva, O. (2017) · Current Molecular Medicine · doi:10.2174/1566524017666170807144946 · Cited by 50 · see citing works
Che, Q., Liu, B., Wang, F., He, Y., Lu, W., Liao, Y. J., Gu, W. T., & Wan, X. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.080 · Cited by 50 · see citing works
Zhang, K., Huang, X., Li, X., Feng, M., Li, L., Cai, X., Zhang, C., Liu, X., Zhang, M., Zhang, Y., et al. (2012) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2012.09.007 · Cited by 50 · see citing works
Béguinot, M., Dauplat, M.-M., Kwiatkowski, F., Lebouëdec, G., Tixier, L., Pomel, C., Penault-Llorca, F. M., & Radosevic‐Robin, N. (2018) · BMC Cancer · doi:10.1186/s12885-018-4013-6 · Cited by 49 · see citing works
Zhou, Q., Jin, P., Liu, J., Li, S., Liu, W., & Xi, S. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.111693 · Cited by 48 · see citing works
Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells
Ogawa, H., Koyanagi‐Aoi, M., Otani, K., Zen, Y., Maniwa, Y., & Aoi, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-12017-y · Cited by 47 · see citing works
Effect of Cellular Senescence on the Growth of HER2-Positive Breast Cancers
Fluck, M. F. Z., Morancho, B., Vicario, R., Luque-García, A., Escorihuela, M., Villanueva, J., Rubio, I. T., & Arribas, J. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv020 · Cited by 45 · see citing works
Ren, Y. T., Zhou, X., Liu, X., Jia, H.-H., Zhao, X., Wang, Q.-X., Han, L., Song, X., Zhu, Z.-Y., Sun, T., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.02.003 · Cited by 45 · see citing works
Challenging a Misnomer? The Role of Inflammatory Pathways in Inflammatory Breast Cancer
Morrow, R. J., Etemadi, N., Yeo, B., & Ernst, M. (2017) · Mediators of Inflammation · doi:10.1155/2017/4754827 · Cited by 38 · see citing works
A Bispecific HER2-Targeting FynomAb with Superior Antitumor Activity and Novel Mode of Action
Brack, S., Attinger-Toller, I., Schade, B., Mourlane, F., Klupsch, K., Woods, R., Hachemi, H., von der Bey, U., Koenig-Friedrich, S., Bertschinger, J., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0046-t · Cited by 43 · see citing works
GP130 Cytokines in Breast Cancer and Bone
Omokehinde, T., & Johnson, R. W. (2020) · Cancers · doi:10.3390/cancers12020326 · Cited by 42 · see citing works
Hsiao, Y.-C., Yeh, M., Chen, Y., Liu, J., Tang, C., & Huang, W. (2015) · Oncotarget · doi:10.18632/oncotarget.5700 · Cited by 39 · see citing works
Bak, Y., Kwon, T., Bak, I. S., Hong, J. T., Yu, D., & Yoon, D. (2016) · Oncotarget · doi:10.18632/oncotarget.7007 · Cited by 39 · see citing works
Qiu, Y., Yang, L., Liu, H., & Luo, X. (2021) · Stem Cells · doi:10.1002/stem.3381 · Cited by 39 · see citing works
PAD2 Overexpression in Transgenic Mice Promotes Spontaneous Skin Neoplasia
McElwee, J. L., Mohanan, S., Horibata, S., Sams, K. L., Anguish, L. J., McLean, D. T., Cvitaš, I., Wakshlag, J. J., & Coonrod, S. A. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0749 · Cited by 38 · see citing works
Haan, J. C., Bhaskaran, R., Ellappalayam, A., Bijl, Y., Griffioen, C. J., Lujinovic, E., Audeh, W. M., Penault-Llorca, F. M., Mittempergher, L., & Glas, A. M. (2021) · Genes Chromosomes and Cancer · doi:10.1002/gcc.23014 · Cited by 38 · see citing works
Microenvironment, Oncoantigens, and Antitumor Vaccination: Lessons Learned from BALB-neuT Mice
Conti, L., Ruiu, R., Barutello, G., Macagno, M., Bandini, S., Cavallo, F., & Lanzardo, S. (2014) · BioMed Research International · doi:10.1155/2014/534969 · Cited by 35 · see citing works
Trotter, T. N., Shuptrine, C. W., Tsao, L.-C., Marek, R. D., Acharya, C. R., Wei, J.-P., Yang, X., Lei, G., Wang, T., Lyerly, H. K., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-18-3825 · Cited by 34 · see citing works
Self-citationInterplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells
Castellana, B., Aasen, T., Moreno‐Bueno, G., Dunn, S. E., & y Cajal, S. R. (2015) · Oncotarget · doi:10.18632/oncotarget.5664 · Cited by 33 · see citing works
Licznerska, B. E., Szaefer, H., Wierzchowski, M., Sobierajska, H., & Baer‐Dubowska, W. (2016) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-016-2871-2 · Cited by 32 · see citing works
Du, L., Chang, H., Xu, W., Wei, Y., Wang, Y., Yin, L., & Zhang, X. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118217 · Cited by 31 · see citing works
Koellensperger, E., Gramley, F., Preisner, F., Leimer, U., Germann, G., & Dexheimer, V. (2014) · Stem Cell Research & Therapy · doi:10.1186/scrt454 · Cited by 31 · see citing works
Huang, W., Hung, C., Wei, C., Chen, T.-M., Chien, P., Pan, H., Lin, Y.-M., & Chen, Y. (2016) · Oncotarget · doi:10.18632/oncotarget.11471 · Cited by 31 · see citing works
Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
Brufsky, A. (2014) · Breast Cancer Basic and Clinical Research · doi:10.4137/bcbcr.s9453 · Cited by 29 · see citing works
HER2-driven breast cancer suppression by the JNK signaling pathway
Itah, Z., Chaudhry, S., Ponny, S. R., Aydemir, Ö., Lee, A., Cavanagh, J., Tournier, C., Muller, W. J., & Davis, R. J. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2218373120 · Cited by 28 · see citing works
Zhao, S., Ohara, S., Kanno, Y., Midorikawa, Y., Nakayama, M., Makimura, M., Park, Y., & Inouye, Y. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.11.021 · Cited by 28 · see citing works
Kearney, M., Franks, L. E., Lee, S. Y., Tiersten, A., Makower, D., Cigler, T., Mundi, P. S., Chi, D.-C., Goel, A., Klein, P., et al. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06306-4 · Cited by 27 · see citing works
The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer
Martínez-Pérez, C., Kay, C., Meehan, J., Gray, M., Dixon, J. M., & Turnbull, A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111073 · Cited by 27 · see citing works
Ali, A. M., Gómez‐Biagi, R. F., Rosa, D. A., Lai, P., Heaton, W. L., Park, J. S., Eiring, A. M., Vellore, N. A., de Araujo, E. D., Ball, D. P., et al. (2016) · ChemMedChem · doi:10.1002/cmdc.201600021 · Cited by 27 · see citing works
Tumor dormancy and the neuroendocrine system: an undisclosed connection?
Zappalà, G., Green, P. A., & Cole, S. W. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9400-x · Cited by 27 · see citing works
Andreasen, S., Therkildsen, M., Grauslund, M., Friis-Hansen, L., Wessel, I., & Homøe, P. (2015) · Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS) · doi:10.1111/apm.12407 · Cited by 26 · see citing works
Orfanou, I.-M., Argyros, O., Papapetropoulos, A., Tseleni‐Balafouta, S., Vougas, K. N., & Tamvakopoulos, C. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.608201 · Cited by 25 · see citing works
Improving drug penetration to curb tumor drug resistance
Marcucci, F., & Corti, A. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.06.004 · Cited by 25 · see citing works
Thrombocytosis as a prognostic factor in inflammatory breast cancer
Harano, K., Kogawa, T., Wu, J., Yuan, Y., Cohen, E. N., Lim, B., Reuben, J. M., & Ueno, N. T. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4463-6 · Cited by 25 · see citing works
Noncoding RNAs that associate with YB-1 alter proliferation in prostate cancer cells
Liu, T. T., Arango-Argoty, G., Li, Z., Lin, Y., Kim, S. W., Dueck, A., Ozsolak, F., Monaghan, A. P., Meister, G., DeFranco, D. B., et al. (2015) · RNA · doi:10.1261/rna.045559.114 · Cited by 21 · see citing works
Clark, D. A., Dmetrichuk, J. M., McCready, M. E., Dhesy‐Thind, S., & Arredondo, J. L. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12665 · Cited by 18 · see citing works
Cantini, L., Pistelli, M., Merloni, F., Fontana, A., Bertolini, I., Angelis, C. D., Bastianelli, L., Mora, A. D., Santinelli, A., Savini, A., et al. (2019) · Clinical Breast Cancer · doi:10.1016/j.clbc.2019.06.008 · Cited by 17 · see citing works
Makhlin, I., McAndrew, N. P., Wileyto, E. P., Clark, A. S., Holmes, R., Bottalico, L. N., Mesaros, C., Blair, I. A., Jeschke, G. R., Fox, K. R., et al. (2022) · npj Breast Cancer · doi:10.1038/s41523-022-00487-x · Cited by 16 · see citing works
Liu, X., Cao, X., Liu, C., Cao, Y., Zhao, Q., Tan, X., Li, X., Xu, X., Yu, E., & Wang, H. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.36916 · Cited by 16 · see citing works
Cytokines in various molecular subtypes of breast cancer
Autenshlyus, A. I., Давлетова, К. И., Анатольевич, В. Н., Marinkin, I. O., & Lyakhovich, V. V. (2021) · International Journal of Immunopathology and Pharmacology · doi:10.1177/20587384211034089 · Cited by 14 · see citing works
Lapatinib inhibits doxorubicin induced migration of HER2-positive breast cancer cells
Chintalaramulu, N., Vadivelu, R. K., Nguyen, N., & Cock, I. E. (2020) · Inflammopharmacology · doi:10.1007/s10787-020-00711-9 · Cited by 14 · see citing works
Kanzaki, H., Mukhopadhya, N. K., Cui, X., Ramanujan, V. K., & Murali, R. (2016) · Monoclonal Antibodies in Immunodiagnosis and Immunotherapy · doi:10.1089/mab.2015.0056 · Cited by 13 · see citing works
Morrow, R. J., Allam, A. H., Yeo, B. J., Deb, S., Murone, C., Lim, E., Johnstone, C. N., & Ernst, M. (2022) · Cancers · doi:10.3390/cancers14092292 · Cited by 13 · see citing works
Kubatka, P., Huniadi, M., Kapinová, A., Nosálová, N., Varghese, E., Blahútová, D., Horňák, S., Trbolova, A., Biringer, K., Adamicová, K., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.10.067 · Cited by 12 · see citing works
Sakai, J., Yang, J., Chou, C.-K., Wu, W. W., & Akkoyunlu, M. (2023) · eLife · doi:10.7554/elife.83561 · Cited by 9 · see citing works
In vivo modeling of the EGFR family in breast cancer progression and therapeutic approaches
Simond, A. M., & Muller, W. J. (2020) · Advances in cancer research · doi:10.1016/bs.acr.2020.04.004 · Cited by 11 · see citing works
- Authors
- Hartman, Z. C., Yang, X.-Y., Glass, O., Lei, G., Osada, T., Dave, S. S., Morse, M. A., Clay, T. M., & Lyerly, H. K.
- Affiliations
- Duke University (US)
- Authors' Affiliations: 1Duke Comprehensive Cancer Center, Departments of Surgery, 2Medicine, and 3Immunology, Duke University Medical Center, Durham, North Carolina
- Venue
- Cancer Research
- Published
- 2011-06-30
- Volume
- 71
- Issue
- 13
- Pages
- 4380-4391
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3129398
- OpenAlex
- W2103315206
- Cited by
- 137
- References
- 41
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 5 · 2018: 7 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 13
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA95447, P01CA078673, BC050221, R01CA095447, P50 CA89496-01, P30CA014236)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- HER2 overexpression, breast cancer, interleukin-6, STAT3 signaling, autocrine signaling, systemic inflammation, carcinogenesis, HER2 mutation, inflammatory gene expression
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Inflammation, Mice, Inbred BALB C, Phosphorylation, Transcription Factors, Signal Transduction, Interleukin-6, Up-Regulation, Gene Expression Regulation, Neoplastic, 3T3 Cells, Mice, SCID, Mice, Inbred NOD, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Cell Line, Tumor, Cell Growth Processes, STAT3 Transcription Factor, Mice
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
