Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth
Open accessAbstract
Colorectal carcinoma (CRC) is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRC-derived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
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IL-6 via STAT-3 promotes tumor cell proliferation in many cancers, including oral squamous cell carcinoma via DNA hypomethylation, prostate cancer through androgen receptor activation, and colon cancer.
“IL-6 via STAT-3 has been shown to promote tumor cell proliferation in many cancers, including oral squamous cell carcinoma via DNA hypomethylation (31), prostate cancer through androgen receptor activation (32), and colon cancer (33).”
From Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis (2021) · cites this paper as [33]
Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.
“Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.58,69–73”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [69]
Cites
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790 · see citing works
Bowman, T., Garcia, R., Turkson, J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1203527 · Cited by 1,743 · see citing works
Targeted disruption of the mouse <i>Stat3</i> gene leads to early embryonic lethality
Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., & Akira, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3801 · Cited by 1,323 · see citing works
O’Shea, J. J., Gadina, M., & Schreiber, R. D. (2002) · Cell · doi:10.1016/s0092-8674(02)00701-8 · Cited by 1,119 · see citing works
Akira, S., Nishio, Y., Inoue, M., Wang, X.-J., We, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M., & Kishimoto, T. (1994) · Cell · doi:10.1016/0092-8674(94)90235-6 · Cited by 1,019 · see citing works
Ory, D., Neugeboren, B. I., & Mulligan, R. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11400 · Cited by 926 · see citing works
Levy, D., & Lee, C.-K. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15650 · Cited by 925 · see citing works
Bromberg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15617 · Cited by 846 · see citing works
Garcia, R., Bowman, T. L., Niu, G., Yu, H., Minton, S., Muro‐Cacho, C., Cox, C. E., Falcone, R., Fairclough, R., Parsons, S. J., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204349 · Cited by 747 · see citing works
Levy, D. E., & Lee, C.-K. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215650 · Cited by 734 · see citing works
Epling-Burnette, P. K., Liu, J. H., Catlett-Falcone, R., Turkson, J., Oshiro, M., Kothapalli, R., Li, Y., Wang, J.-M., Yang-Yen, H.-F., Karras, J., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci9940 · Cited by 633 · see citing works
Mora, L. B., Buettner, R., Seigne, J. D., Diaz, J. I., Ahmad, N., Garcia, R., Bowman, T. L., Falcone, R., Fairclough, R., Cantor, A. B., et al. (2002) · PubMed · Cited by 532 · see citing works
Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., & Takeda, J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.17.4657 · Cited by 519 · see citing works
Grandis, J. R., Drenning, S. D., Chakraborty, A., Zhou, M. Y., Zeng, Q., Pitt, A. S., & Tweardy, D. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3785 · Cited by 507 · see citing works
Roles of activated Src and Stat3 signaling in melanoma tumor cell growth
Niu, G., Bowman, T., Huang, M., Shivers, S., Reintgen, D., Daud, A., Chang, A., Kraker, A., Jove, R., & Yu, H. (2002) · Oncogene · doi:10.1038/sj.onc.1205859 · Cited by 432 · see citing works
Rahaman, S. O., Harbor, P. C., Chernova, O., Barnett, G. H., Vogelbaum, M. A., & Haque, S. J. (2002) · Oncogene · doi:10.1038/sj.onc.1206047 · Cited by 377 · see citing works
Masuda, M., Suzui, M., Yasumatu, R., Nakashima, T., Kuratomi, Y., Azuma, K., Tomita, K., Komiyama, S., & Weinstein, I. B. (2002) · PubMed · Cited by 376 · see citing works
Apc modulates embryonic stem-cell differentiation by controlling the dosage of β-catenin signaling
Kielman, M. F., Rindapää, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M. M., Roberts, S., Smits, R., & Fodde, R. (2002) · Nature Genetics · doi:10.1038/ng1045 · Cited by 362 · see citing works
Interleukin-6 Is an Autocrine Growth Factor in Human Prostate Cancer
Giri, D., Özen, M., & Ittmann, M. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63067-2 · Cited by 331 · see citing works
Real, P. J., Sierra, A., de Juan, A., Segovia, J. C., Lopez-Vega, J. M., & Fernandez-Luna, J. L. (2002) · Oncogene · doi:10.1038/sj.onc.1206004 · Cited by 321 · see citing works
GENETIC AND EPIGENETIC ALTERATIONS IN COLON CANCER
Grady, W. M., & Markowitz, S. D. (2002) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.3.022502.103043 · Cited by 316 · see citing works
Niu, G., Heller, R. F., Catlett-Falcone, R., Coppola, D., Jaroszeski, M. J., Dalton, W. S., Jove, R., & Yu, H. (1999) · PubMed · Cited by 313 · see citing works
Wnt/Beta-Catenin/Tcf Signaling: A Critical Pathway in Gastrointestinal Tumorigenesis
Kolligs, F. T., Bommer, G. T., & Göke, B. (2002) · Digestion · doi:10.1159/000066755 · Cited by 312 · see citing works
Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells
Burke, W. M., Jin, X., Lin, H.-J. L., Huang, M., Liu, R., Reynolds, R. K., & Lin, J. (2001) · Oncogene · doi:10.1038/sj.onc.1204990 · Cited by 269 · see citing works
Shen, Y., Devgan, G., Darnell, J. E., & Bromberg, J. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1543 · Cited by 249 · see citing works
Schuringa, J., Wierenga, A., Kruijer, W., & Vellenga, E. (2000) · Blood · doi:10.1182/blood.v95.12.3765 · Cited by 213 · see citing works
Epling‐Burnette, P. K., Zhong, B., Bai, F., Jiang, K., Bailey, R. D., Garcia, R., Jove, R., Djeu, J. Y., Loughran, T. P., & Wei, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7486 · Cited by 181 · see citing works
Beneklı, M., Xia, Z., Donohue, K. A., Ford, L. A., Pixley, L. A., Baer, M. R., Baumann, H., & Wetzler, M. (2002) · Blood · doi:10.1182/blood.v99.1.252 · Cited by 180 · see citing works
Stat3 Controls Cell Movements during Zebrafish Gastrulation
Yamashita, S., Miyagi, C., Carmany-Rampey, A., Shimizu, T., Fujii, R., Schier, A. F., & Hirano, T. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00126-0 · Cited by 178 · see citing works
Schaefer, L. K., Ren, Z., Fuller, G. N., & Schaefer, T. S. (2002) · Oncogene · doi:10.1038/sj.onc.1205263 · Cited by 170 · see citing works
Activation of Signal Transducer and Activator of Transcription 3 in Renal Cell Carcinoma:
Horiguchi, A., Oya, M., Shimada, T., Uchida, A., Marumo, K., & Murai, M. (2002) · The Journal of Urology · doi:10.1016/s0022-5347(05)64741-6 · Cited by 166 · see citing works
Kortylewski, M., Heinrich, P., Mackiewicz, A., Schniertshauer, U., Klingmüller, U., Nakajima, K., Hirano, T., Horn, F., & Behrmann, I. (1999) · Oncogene · doi:10.1038/sj.onc.1202708 · Cited by 146 · see citing works
Stat3 activation in prostatic carcinomas
Dhir, R., Ni, Z., Lou, W., DeMiguel, F., Grandis, J. R., & Gao, A. C. (2002) · The Prostate · doi:10.1002/pros.10079 · Cited by 135 · see citing works
Molecular causes of colon cancer
Oving, I. M., & Clevers, H. C. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2002.01004.x · Cited by 135 · see citing works
Inhibition of Transcription Factor Stat5 Induces Cell Death of Human Prostate Cancer Cells
Ahonen, T. J., Xie, J., LeBaron, M. J., Zhu, J., Nurmi, M. J., Alanen, K. A., Rui, H., & Nevalainen, M. T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304307200 · Cited by 132 · see citing works
Smith, P. C., & Keller, E. T. (2001) · The Prostate · doi:10.1002/pros.1080 · Cited by 117 · see citing works
Widschwendter, A., Geymayer, S., Welte, T., Daxenbichler, G., Marth, C., & Doppler, W. (2002) · PubMed · Cited by 107 · see citing works
Autocrine-mediated Activation of STAT3 Correlates with Cell Proliferation in Breast Carcinoma Lines
Li, L., & Shaw, P. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109962200 · Cited by 102 · see citing works
Modern laser scanning microscopy in biology, biotechnology and medicine
Kj, H., & König, K. (2003) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/s0940-9602(03)80002-x · Cited by 102 · see citing works
Autocrine interleukin-6 production in renal cell carcinoma: evidence for the involvement of p53.
Angelo, L. S., Talpaz, M., & Kurzrock, R. (2002) · PubMed · Cited by 91 · see citing works
The Interleukin-4 Receptor Activates STAT5 by a Mechanism That Relies upon Common γ-Chain
Lischke, A., Moriggl, R., Brändlein, S., Berchtold, S., Kammer, W., Sebald, W., Groner, B., Liu, X., Hennighausen, L. G., & Friedrich, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.47.31222 · Cited by 78 · see citing works
Self-citationDifferential function of STAT5 isoforms in head and neck cancer growth control
Leong, P. L., Xi, S., Drenning, S. D., Dyer, K. F., Wentzel, A. L., Lerner, E. C., Smithgall, T. E., & Grandis, J. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205385 · Cited by 72 · see citing works
Homodimerization of Interleukin-4 Receptor α Chain Can Induce Intracellular Signaling
Kammer, W., Lischke, A., Moriggl, R., Groner, B., Ziemiecki, A., Gurniak, C. B., Berg, L. J., & Friedrich, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.39.23634 · Cited by 72 · see citing works
Self-citationHsi, L. C., Angerman‐Stewart, J., & Eling, T. E. (1999) · Carcinogenesis · doi:10.1093/carcin/20.11.2045 · Cited by 70 · see citing works
Genetic instability in human mismatch repair deficient cancers
Duval, A., & Hamelin, R. (2002) · Annales de Génétique · doi:10.1016/s0003-3995(02)01115-2 · Cited by 69 · see citing works
Vécsey-Semjén, B., Becker, K., Sinski, A., Blennow, E., Vietor, I., Zatloukal, K., Beug, H., Wagner, E., & Huber, L. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205577 · Cited by 60 · see citing works
Self-citationEvaluation of telomerase in the development and progression of colon cancer
Boldrini, L., Faviana, P., Gisfredi, S., Zucconi, Y., Quirico, D. D., Donati, V. L., Berti, P., Spisni, R., Galleri, D., Materazzi, G., et al. (2002) · International Journal of Molecular Medicine · doi:10.3892/ijmm.10.5.589 · Cited by 36 · see citing works
Ma, A., Xia, L. P., Littman, S. J., Swinler, S. E., Lader, G., Polinkovsky, A., Olechnowicz, J., Kasturi, L., Lutterbaugh, J., Modrich, P. L., et al. (2000) · Oncogene · doi:10.1038/sj.onc.1203568 · Cited by 30 · see citing works
CELLULAR SIGNALLING PATHWAYS: NEW TARGETS IN LEUKAEMIA THERAPY
Ravandi, F., Talpaz, M., Kantarjian, H. M., & Estrov, Z. E. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03236.x · Cited by 25 · see citing works
Constitutive Activation of Stat1 and Stat3 in Primary Erythroleukemia Cells
Kirito, K., Nagashima, T., Ozawa, K., & Komatsu, N. (2002) · International Journal of Hematology · doi:10.1007/bf02981979 · Cited by 24 · see citing works
Colorectal cancer screening and follow-up
Fleming, R. (1998) · Surgical Oncology · doi:10.1016/s0960-7404(99)00034-1 · Cited by 16 · see citing works
Norris, A. L., Clissold, P. M., Askham, J. M., Morrison, E. E., Moncur, P. H., McCall, S. H., Coletta, P. L., Meredith, D. M., & Markham, A. F. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00305-6 · Cited by 3 · see citing works
Flagged first, then by citations
6 of the 59 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors
Siveen, K. S., Sikka, S., Surana, R., Dai, X., Zhang, J., Kumar, A. P., Tan, B. K. H., Sethi, G., & Bishayee, A. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.12.005 · Cited by 637 · see citing works
Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis
Gibbs, C. P., Kukekov, V. G., Reith, J. D., Tchigrinova, O., Suslov, O. N., Scott, E. W., Ghivizzani, S. C., Ignatova, T. N., & Steindler, D. A. (2005) · Neoplasia · doi:10.1593/neo.05394 · Cited by 492 · see citing works
Tumor exosomes inhibit differentiation of bone marrow dendritic cells
Yu, S., Liu, C., Su, K., Wang, J., Liu, Y., Zhang, L., Li, C., Cong, Y., Kimberly, R., Grizzle, W. E., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6867 · Cited by 425 · see citing works
Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention
Colussi, D., Brandi, G., Bazzoli, F., & Ricciardiello, L. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140816365 · Cited by 429 · see citing works
Interleukin-6 - A Key Regulator of Colorectal Cancer Development
Waldner, M., Foersch, S., & Neurath, M. (2012) · International Journal on Biological Sciences · doi:10.7150/ijbs.4614 · Cited by 422 · see citing works
Kartikasari, A. E. R., Huertas, C. S., Mitchell, A., & Plebanski, M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.692142 · Cited by 343 · see citing works
“IL-6 via STAT-3 has been shown to promote tumor cell proliferation in many cancers, including oral squamous cell carcinoma via DNA hypomethylation (31), prostate cancer through androgen receptor activation (32), and colon cancer (33).”
BackgroundLi, Y., de Haar, C., Chen, M., Deuring, J., Gerrits, M. M., Smits, R., Xia, B., Kuipers, E. J., & van der Woude, C. J. (2010) · Gut · doi:10.1136/gut.2009.184176 · Cited by 339 · see citing works
Pechkovsky, D. V., Prasse, A., Kollert, F., Engel, K. M., Dentler, J., Luttmann, W., Friedrich, K., Müller–Quernheim, J., & Zissel, G. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.06.017 · Cited by 328 · see citing works
Self-citationSmad4 signalling in T cells is required for suppression of gastrointestinal cancer
Kim, B., Li, C., Qiao, W., Mamura, M., Kasperczak, B., Anver, M. R., Wolfraim, L. A., Hong, S., Mushinski, E. B., Potter, M., et al. (2006) · Nature · doi:10.1038/nature04846 · Cited by 320 · see citing works
Cancer stem cells in colorectal cancer: a review
Munro, M. J., Wickremesekera, S. K., Peng, L., Tan, S. T., & Itinteang, T. (2017) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2017-204739 · Cited by 301 · see citing works
STAT3 Is Necessary for Proliferation and Survival in Colon Cancer–Initiating Cells
Lin, L., Liu, A., Peng, Z., Lin, H.-J. L., Li, P., Li, C., & Lin, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4660 · Cited by 297 · see citing works
Highlighted STAT3 as a potential drug target for cancer therapy
Lee, H., Jeong, A. J., & Ye, S. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.7.152 · Cited by 294 · see citing works
STAT‐mediated EGFR signaling in cancer
Quesnelle, K. M., Boehm, A. L., & Grandis, J. R. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21475 · Cited by 295 · see citing works
Immunotherapy, Inflammation and Colorectal Cancer
Lichtenstern, C. R., Ngu, R. K., Shalapour, S., & Karin, M. (2020) · Cells · doi:10.3390/cells9030618 · Cited by 290 · see citing works
Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention
Xiong, A., Yang, Z., Shen, Y., Zhou, J., & Shen, Q. (2014) · Cancers · doi:10.3390/cancers6020926 · Cited by 283 · see citing works
Regulation of translocator protein 18kDa (TSPO) expression in health and disease states☆
Batarseh, A. M., & Papadopoulos, V. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.06.013 · Cited by 271 · see citing works
Targeting transcription factor STAT3 for cancer prevention and therapy
Chai, E. Z. P., Shanmugam, M. K., Arfuso, F., Dharmarajan, A., Wang, C., Kumar, A. P., Samy, R. P., Lim, L. H. K., Wang, L., Goh, B. C., et al. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.10.004 · Cited by 265 · see citing works
NF-κB pathways in the development and progression of colorectal cancer
Patel, M., Horgan, P. G., McMillan, D. C., & Edwards, J. (2018) · Translational research · doi:10.1016/j.trsl.2018.02.002 · Cited by 251 · see citing works
Anticancer Activity of Curcumin and Its Analogues: Preclinical and Clinical Studies
Allegra, A., Innao, V., Russo, S., Gerace, D. G., Alonci, A., & Musolino, C. (2016) · Cancer Investigation · doi:10.1080/07357907.2016.1247166 · Cited by 239 · see citing works
Ups and downs: The STAT1:STAT3 seesaw of Interferon and gp130 receptor signalling
Regis, G., Pensa, S., Boselli, D., Novelli, F., & Poli, V. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.06.004 · Cited by 237 · see citing works
Bhat, A. A., Nisar, S., Singh, M. K., Ashraf, B., Masoodi, T., Prasad, C. P., Sharma, A., Maacha, S., Karedath, T., Hashem, S., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12295 · Cited by 245 · see citing works
Inflammatory cytokines in the pathogenesis of cardiovascular disease and cancer
Amin, M. N., Siddiqui, S. A., Ibrahim, M., Hakim, M. L., Ahammed, M. S., Kabir, A., & Sultana, F. (2020) · SAGE Open Medicine · doi:10.1177/2050312120965752 · Cited by 236 · see citing works
Deng, L., Zhou, J.-F., Sellers, R. S., Li, J.-F., Nguyen, A., Wang, Y., Orlofsky, A., Liu, Q., Hume, D. A., Pollard, J. W., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090622 · Cited by 228 · see citing works
Farha, A. K., Gan, R., Li, H., Wu, D., Atanasov, A. G., Gul, K., Zhang, J.-R., Yang, Q., & Corke, H. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1829541 · Cited by 226 · see citing works
Foshay, K. M., & Gallicano, G. I. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.11.016 · Cited by 225 · see citing works
Cytokine-Induced Modulation of Colorectal Cancer
Mager, L. F., Wasmer, M.-H., Rau, T. T., & Krebs, P. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00096 · Cited by 215 · see citing works
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T
Zhang, X., Guo, A., Yu, J., Possemato, A. P., Chen, Y., Zheng, W., Polakiewicz, R. D., Kinzler, K. W., Vogelstein, B., Velculescu, V. E., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611665104 · Cited by 210 · see citing works
Small Molecule Inhibitors of Signal Transducer and Activator of Transcription 3 (Stat3) Protein
Debnath, B., Xu, S., & Neamati, N. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300207s · Cited by 205 · see citing works
Morikawa, T., Baba, Y., Yamauchi, M., Kuchiba, A., Nosho, K., Shima, K., Tanaka, N., Huttenhower, C., Frank, D. A., Fuchs, C. S., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2694 · Cited by 199 · see citing works
Lee, E., Fertig, E. J., Jin, K., Sukumar, S., Pandey, N. B., & Popel, A. S. (2014) · Nature Communications · doi:10.1038/ncomms5715 · Cited by 197 · see citing works
Ursolic acid, a potential anticancer compound for breast cancer therapy
Yin, R., Li, T., Tian, J., Xi, P., & Liu, R. H. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2016.1203755 · Cited by 192 · see citing works
Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development
Waldner, M. J., & Neurath, M. F. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2013.12.003 · Cited by 193 · see citing works
STAT3 and apoptosis challenges in cancer
Fathi, N., Rashidi, G., Khodadadi, A., Shahi, S., & Sharifi, S. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.05.121 · Cited by 189 · see citing works
Mishra, J., Drummond, J., Quazi, S. H., Karanki, S. S., Shaw, J., Chen, B., & Kumar, N. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2012.09.014 · Cited by 179 · see citing works
Stat3 Is a Negative Regulator of Intestinal Tumor Progression in ApcMin Mice
Musteanu, M., Blaas, L., Mair, M., Schlederer, M., Bilban, M., Tauber, S., Esterbauer, H., Mueller, M., Casanova, E., Kenner, L., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.11.049 · Cited by 166 · see citing works
Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030
Lü, L., Liu, Y., Li, H., Li, P., Fuchs, J. R., Shibata, H., Iwabuchi, Y., & Lin, J. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.200 · Cited by 165 · see citing works
Degagné, É., Pandurangan, A. K., Bandhuvula, P., Kumar, A., Eltanawy, A., Zhang, M., Yoshinaga, Y., Nefedov, M. D., de Jong, P. J., Fong, L. G., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74188 · Cited by 155 · see citing works
Zhang, Z., Duan, Q., Zhao, H., Liu, T., Wu, H., Shen, Q., Wang, C., & Yin, T. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.08.023 · Cited by 153 · see citing works
The role of IL-21 in immunity and cancer
Davis, M. R., Zhu, Z., Hansen, D. M., Bai, Q., & Fang, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2014.12.047 · Cited by 151 · see citing works
Lin, L., Deangelis, S., Foust, E., Fuchs, J. R., Li, C., Li, P., Schwartz, E. B., Lesinski, G. B., Benson, D., Lü, J., et al. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-217 · Cited by 149 · see citing works
Zhang, J.-F., He, M., Fu, W.-M., Wang, H., Chen, L., Zhu, X. M., Chen, Y., Xie, D., Lai, P. B. S., Chen, G., et al. (2010) · Hepatology · doi:10.1002/hep.24595 · Cited by 145 · see citing works
Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?
Beebe, J., Liu, J., & Zhang, J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.006 · Cited by 142 · 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
Tsareva, S. A., Moriggl, R., Corvinus, F. M., Wiederanders, B., Schütz, A., Kovačic, B., & Friedrich, K. (2007) · Neoplasia · doi:10.1593/neo.06820 · Cited by 137 · see citing works
Self-citationThe many faces of Janus kinase
Seavey, M. M., & Dobrzański, P. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.12.024 · Cited by 135 · see citing works
Rosen, D. G., Mercado‐Uribe, I., Yang, G. S., Bast, R. C., Amin, H. M., Lai, R. L., & Liu, J. (2006) · Cancer · doi:10.1002/cncr.22293 · Cited by 133 · see citing works
MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer
Cekaite, L., Rantala, J., Bruun, J., Guriby, M., Ågesen, T. H., Danielsen, S. A., Lind, G. E., Nesbakken, A., Kallioniemi, O., Lothe, R. A., et al. (2012) · Neoplasia · doi:10.1593/neo.121094 · Cited by 133 · see citing works
The role of the interleukin (IL)-6/IL-6 receptor axis in cancer.
Taher, M. Y., Davies, D., & Maher, J. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180136 · Cited by 115 · 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
Self-citationSpitzner, M., Roesler, B., Bielfeld, C., Emons, G., Gaedcke, J., Wolff, H. A., Rave‐Fränk, M., Kramer, F., Beissbarth, T., Kitz, J., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.28429 · Cited by 128 · see citing works
Early-onset colorectal cancer: A sporadic or inherited disease?
Stigliano, V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i35.12420 · Cited by 129 · see citing works
Yao, C., Su, L., Shan, J., Zhu, C., Liu, L., Liu, C., Xu, Y., Yang, Z., Bian, X., Shao, J., et al. (2016) · Stem Cells · doi:10.1002/stem.2320 · Cited by 123 · see citing works
Shalaby, A. A., Presneau, N., Ye, H., Halai, D., Berisha, F., Idowu, B. D., Leithner, A., Liegl, B., Briggs, T. W. R., Bácsi, K., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2818 · Cited by 118 · see citing works
Lin, L., Fuchs, J. R., Li, C., Olson, V., Bekaii‐Saab, T., & Lin, J. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.10.112 · Cited by 117 · see citing works
Augmented gp130‐mediated cytokine signalling accompanies human gastric cancer progression
Cb, J., Judd, L. M., Menheniott, T. R., Kronborg, I., Dow, C., Yeomans, N. D., Boussioutas, A., Robb, L. G., & Giraud, A. (2007) · The Journal of Pathology · doi:10.1002/path.2218 · Cited by 117 · see citing works
Targeting STAT3 Signaling Pathway in Colorectal Cancer
Gargalionis, A. N., Papavassiliou, K. A., & Papavassiliou, A. G. (2021) · Biomedicines · doi:10.3390/biomedicines9081016 · Cited by 113 · see citing works
The regulatory roles of phosphatases in cancer
Stebbing, J., Lit, L. C., Zhang, H., Darrington, R. S., Melaiu, O., Rudraraju, B., & Giamas, G. (2013) · Oncogene · doi:10.1038/onc.2013.80 · Cited by 112 · see citing works
Ziesché, E., Bachmann, M., Kleinert, H., Pfeilschifter, J. M., & Mühl, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611040200 · Cited by 113 · see citing works
Laßmann, S., Schuster, I., Walch, A. K., Göbel, H., Jütting, U., Makowiec, F., Hopt, U. T., & Werner, M. (2007) · Journal of Clinical Pathology · doi:10.1136/jcp.2005.035113 · Cited by 112 · see citing works
Molecular mechanisms in colitis-associated colorectal cancer
Zhou, R. W., Harpaz, N., Itzkowitz, S. H., & Parsons, R. E. (2023) · Oncogenesis · doi:10.1038/s41389-023-00492-0 · Cited by 118 · see citing works
Myeloid-Derived Suppressor Cells in Colorectal Cancer
Siemińska, I., & Baran, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01526 · Cited by 108 · see citing works
Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells
Silva, V. R., Santos, L. D. S., Dias, R. B., Quadros, C. A., & Bezerra, D. P. (2021) · 癌症：英文版 · doi:10.1002/cac2.12235 · Cited by 106 · see citing works
Kundu, J., Choi, B. Y., Jeong, C., Kundu, J. K., & Chun, K. (2014) · Oncology Reports · doi:10.3892/or.2014.3223 · Cited by 106 · see citing works
Van Schaeybroeck, S., Kalimutho, M., Dunne, P. D., Carson, R., Allen, W., Jithesh, P. V., Redmond, K. L., Sasazuki, T., Shirasawa, S., Blayney, J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.05.032 · Cited by 106 · see citing works
Targeting STAT3 in cancer and autoimmune diseases
Gharibi, T., Babaloo, Z., Hosseini, A., Abdollahpour‐Alitappeh, M., Hashemi, V., Marofi, F., Nejati‐Koshki, K., & Baradaran, B. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173107 · Cited by 104 · see citing works
To, N. B., Nguyen, Y. T.-K., Moon, J. Y., Ediriweera, M. K., & Cho, S. K. (2020) · Nutrients · doi:10.3390/nu12061663 · Cited by 105 · see citing works
Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma
Gordziel, C., Bratsch, J., Moriggl, R., Knösel, T., & Friedrich, K. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.274 · Cited by 102 · see citing works
Self-citationRecent development of transition metal complexes with in vivo antitumor activity
Liang, J., Zhong, H., Yang, G., Vellaisamy, K., Ma, D., & Leung, C. (2017) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2017.06.002 · Cited by 102 · see citing works
Engelsberger, V., Gerhard, M., & Mejías‐Luque, R. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1339750 · Cited by 109 · see citing works
Han, S., Jeong, A. J., Yang, H., Kang, K. B., Lee, H., Yi, E. H., Kim, B., Cho, C., Chung, J. W., Sung, S. H., et al. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.08.039 · Cited by 98 · see citing works
Withaferin-A Inhibits Colon Cancer Cell Growth by Blocking STAT3 Transcriptional Activity
Choi, B. Y., & Kim, B.-W. (2015) · Journal of Cancer Prevention · doi:10.15430/jcp.2015.20.3.185 · Cited by 97 · see citing works
The role of signal transducers and activators of transcription in colon cancer
Klampfer, L. (2007) · Frontiers in bioscience · doi:10.2741/2893 · Cited by 96 · see citing works
Targeting STAT3 in gastric cancer
Giraud, A. S., Menheniott, T. R., & Judd, L. M. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.709238 · Cited by 92 · see citing works
Molecular markers and targets for colorectal cancer prevention
Janakiram, N. B., & Rao, C. V. (2008) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2008.00742.x · Cited by 92 · see citing works
Ye, T., Yang, F., Zhu, Y., Li, Y., Lei, Q., Song, X., Xia, Y., Xiong, Y., Zhang, L., Wang, N., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2016.452 · Cited by 90 · see citing works
Fenton, J. I., Birmingham, J., Hursting, S. D., & Hord, N. G. (2008) · International Journal of Cancer · doi:10.1002/ijc.23436 · Cited by 89 · see citing works
Direct Targeting Options for STAT3 and STAT5 in Cancer
Orlova, A., Wagner, C., de Araujo, E. D., Bajusz, D., Neubauer, H. A., Herling, M., Gunning, P. T., Keserű, G. M., & Moriggl, R. (2019) · Cancers · doi:10.3390/cancers11121930 · Cited by 88 · see citing works
Self-citationCytokine disbalance in common human cancers.
Culig, Z. (2011) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2010.12.010 · Cited by 98 · see citing works
Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis
Kim, M., Baek, M., & Kim, D. J. (2017) · Current Pharmaceutical Design · doi:10.2174/1381612823666170616082125 · Cited by 87 · see citing works
PARK, K.-W., Kundu, J., Chae, I.-G., Kim, D.-H., Yu, M.-H., Kundu, J. K., & Chun, K. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2281 · Cited by 87 · see citing works
Keeley, T. S., Costanzo-Garvey, D. L., & Cook, L. M. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.10.013 · Cited by 83 · see citing works
Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells
Tomida, M., Ohtake, H., Yokota, T., Kobayashi, Y., & Kurosumi, M. (2008) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-007-0318-6 · Cited by 88 · see citing works
cGAS restricts colon cancer development by protecting intestinal barrier integrity
Hu, S., Fang, Y., Chen, X., Cheng, T., Zhao, M., Du, M., Li, T., Li, M., Zeng, Z., Wei, Y., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105747118 · Cited by 83 · see citing works
Cytokine Induction of Tumor Necrosis Factor Receptor 2 Is Mediated by STAT3 in Colon Cancer Cells
Hamilton, K. E., Simmons, J. G., Ding, S., Landeghem, L. V., & Lund, P. K. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0210 · Cited by 81 · see citing works
Kawasaki, T., Nosho, K., Ohnishi, M., Suemoto, Y., Kirkner, G. J., Dehari, R., Meyerhardt, J. A., Fuchs, C. S., & Ogino, S. (2007) · Neoplasia · doi:10.1593/neo.07334 · Cited by 80 · see citing works
Kesselring, R., Gläsner, J., Hiergeist, A., Naschberger, E., Neumann, H., Brunner, S. M., Wege, A. K., Seebauer, C. T., Köhl, G., Merkl, S., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.03.014 · Cited by 80 · see citing works
Cryptotanshinone, a Stat3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro
Li, W., Saud, S. M., Young, M. R., Colburn, N. H., & Hua, B. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2424-0 · Cited by 80 · see citing works
Kim, D., Park, K., Chae, I. G., Kundu, J., Kim, E., Kundu, J. K., & Chun, K. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22353 · Cited by 79 · see citing works
Spano, J., Milano, G. A., Rixe, C., & Fagard, R. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.07.006 · Cited by 77 · see citing works
Synthesis and Anticancer Evaluation of New 1,3,4-Oxadiazole Derivatives
Stecoza, C. E., Nițulescu, G. M., Draghici, C. C., Căproiu, M. T., Olaru, O. T., Bostan, M., & Mihaila, M. A. (2021) · Pharmaceuticals · doi:10.3390/ph14050438 · Cited by 76 · see citing works
Inflammatory bowel disease and carcinogenesis
Nagao‐Kitamoto, H., Kitamoto, S., & Kamada, N. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10028-4 · Cited by 77 · see citing works
Zheng, W., Wong, K. E., Zhang, Z., Dougherty, U., Mustafi, R., Kong, J., Deb, D. K., Zheng, H., Bissonnette, M., & Li, Y. C. (2011) · International Journal of Cancer · doi:10.1002/ijc.25992 · Cited by 75 · see citing works
CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression
Cui, H., Wang, S., Song, F., Cheng, X., Nan, G., Zhao, Y., Qian, M., Chen, X., Li, J., Liu, F.-L., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00677-2 · Cited by 74 · see citing works
Fang, X., Hong, Y., Dai, L., Qian, Y., Zhu, C., Wu, B., & Li, S. (2017) · Molecular Carcinogenesis · doi:10.1002/mc.22691 · Cited by 73 · see citing works
Ren, R., Sun, H., Ma, C., Liu, J., & Wang, H. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0325-8 · Cited by 73 · see citing works
Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS 3
Singh, S., Chouhan, S., Mohammad, N., & Bhat, M. K. (2017) · FEBS Letters · doi:10.1002/1873-3468.12655 · Cited by 71 · see citing works
Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications
Xu, H., Liu, L., Li, W., Zou, D., Yu, J. Q., Wang, L., & Wong, C. C. (2020) · Oncogene · doi:10.1038/s41388-020-01587-3 · Cited by 70 · see citing works
Therapeutic Targets and Tumor Microenvironment in Colorectal Cancer
Gallo, G., Vescio, G., Paola, G. D., & Sammarco, G. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112295 · Cited by 71 · see citing works
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J. R., Li, P., Lü, J., Li, C., & Lin, J. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3728 · Cited by 71 · see citing works
Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
Saadatdoust, Z., Pandurangan, A. K., Anandasadagopan, S. K., Esa, N. M., Ismail, A., & Mustafa, M. R. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.07.024 · Cited by 70 · see citing works
- Authors
- Corvinus, F. M., Orth, C., Moriggl, R., Tsareva, S. A., Wagner, S., Pfitzner, E. B., Baus, D., Kaufman, R., Huber, L. A., Zatloukal, K., Beug, H., Öhlschläger, P., Schütz, A., Halbhuber, K.-J., & Friedrich, K.
- Affiliations
- Friedrich Schiller University Jena (DE)
- Research Institute of Molecular Pathology (AT)
- Georg Speyer Haus (DE)
- Universität Innsbruck (AT)
- University of Graz (AT)
- Leipzig University (DE)
- Corresponding author
- Friedrich, Karlheinz
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 7
- Issue
- 6
- Pages
- 545-555
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC1501283
- OpenAlex
- W2014737409
- Cited by
- 427
- References
- 59
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 27 · 2023: 21 · 2022: 28 · 2021: 40 · 2020: 29 · 2019: 22 · 2018: 15 · 2017: 27 · 2016: 24 · 2015: 30 · 2014: 24 · 2013: 30 · 2012: 17
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- STAT3, colorectal cancer, constitutive STAT3 activation, interleukin-6, cell proliferation, tumor growth, tumor microenvironment, tumor xenografts, dominant-negative STAT3, therapeutic target, infiltrating lymphocytes
- MeSH terms
- Animals, Biopsy, Cell Differentiation, Colonic Neoplasms, DNA, Genes, Dominant, Humans, Immunohistochemistry, Lymphocytes, Mice, Nude, Neoplasm Transplantation, Retroviridae, Time Factors, Blotting, Western, Colorectal Neoplasms, Signal Transduction, Interleukin-6, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice
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