Interleukin‐6 promotes tumorigenesis by altering DNA methylation in oral cancer cells
Open accessAbstract
Worldwide oral squamous cell carcinoma (OSCC) accounts for more than 100,000 deaths each year. Chronic inflammation constitutes one of the key risk factors for OSCC. Accumulating evidence suggests that aberrant DNA methylation may contribute to OSCC tumorigenesis. This study investigated whether chronic inflammation alters DNA methylation and expression of cancer-associated genes in OSCC. We established an in vitro model of interleukin (IL)-6 mediating chronic inflammation in OSCC cell lines. Thereafter, we measured the ability of IL-6 to induce global hypomethylation of long interspersed nuclear element-1 (LINE-1) sequences, as well as CpG methylation changes using multiple methodologies including quantitative pyrosequencing, methylation-specific multiplex ligation-dependent probe amplification and sensitive melting analysis after real-time-methylation-specific polymerase chain reaction (PCR). Gene expression was investigated by quantitative reverse transcriptase-PCR. IL-6 induced significant global LINE-1 hypomethylation (p=0.016) in our in vitro model of inflammatory stress in OSCC cell lines. Simultaneously, IL-6 induced CpG promoter methylation changes in several important putative tumor suppressor genes including CHFR, GATA5 and PAX6. Methylation changes correlated inversely with the changes in the expression of corresponding genes. Our results indicate that IL-6-induced inflammation promotes tumorigenesis in the oral cavity by altering global LINE-1 hypomethylation. In addition, concurrent hypermethylation of multiple tumor suppressor genes by IL-6 suggests that epigenetic gene silencing may be an important consequence of chronic inflammation in the oral cavity. These findings have clinical relevance, as both methylation and inflammation are suitable targets for developing novel preventive and therapeutic measures.
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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 [31]
The Results report that IL-6 activates STAT3 and induces LINE-1 hypomethylation in oral squamous cell carcinoma cell lines. The Discussion says this may contribute to oral tumorigenesis, but the paper does not establish that hypomethylation promotes tumor-cell proliferation. Citation (31) is attached to the oral-cancer clause; the prostate- and colon-cancer clauses have separate citations. (LLM, conf=0.88)
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Cites
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709 · see citing works
Inflammation and cancer: back to Virchow?
Balkwill, F., & Mantovani, A. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04046-0 · Cited by 7,746 · see citing works
DNA methylation in cancer: too much, but also too little
Ehrlich, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205651 · Cited by 1,540 · see citing works
Epigenetic therapy of cancer: past, present and future
Yoo, C. B., & Jones, P. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1930 · Cited by 1,291 · see citing works
CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future
Esteller, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205600 · Cited by 1,235 · see citing works
The role of STATs in transcriptional control and their impact on cellular function
Bromberg, J., & Darnell, J. E. (2000) · Oncogene · doi:10.1038/sj.onc.1203476 · Cited by 1,201 · see citing works
A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
Yang, A. S. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh032 · Cited by 1,033 · see citing works
Changes in DNA Methylation Patterns in Subjects Exposed to Low-Dose Benzene
Bollati, V., Baccarelli, A., Hou, L., Bonzini, M., Fustinoni, S., Cavallo, D. M., Byun, H., Jiang, J., Marinelli, B., Pesatori, A. C., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2995 · Cited by 612 · see citing works
STAT proteins: From normal control of cellular events to tumorigenesis
Calò, V., Migliavacca, M., Bazan, V., Macaluso, M., Buscemi, M., Gebbia, N., & Russo, A. D. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10364 · Cited by 606 · see citing works
Inhibition of DNA Methylation and Reactivation of Silenced Genes by Zebularine
Cheng, J. C., Matsen, C. B., Gonzales, F. A., Ye, W., Greer, S., Márquez, V. E., Jones, P. A., & Selker, E. U. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.5.399 · Cited by 532 · see citing works
Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy
Choi, S., & Myers, J. N. (2008) · Journal of Dental Research · doi:10.1177/154405910808700104 · Cited by 514 · see citing works
Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies
Botto, L. D., Lin, A. E., Riehle‐Colarusso, T. J., Malik, S., & Correa, A. (2007) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20403 · Cited by 472 · see citing works
Braconi, C., Huang, N., & Patel, T. C. (2009) · Hepatology · doi:10.1002/hep.23381 · Cited by 377 · see citing works
The epigenetics of cancer etiology
Feinberg, A. P. (2004) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2004.06.005 · Cited by 336 · see citing works
Interleukin‐6 predicts recurrence and survival among head and neck cancer patients
Duffy, S. A., Taylor, J. M. G., Terrell, J. E., Islam, M., Li, Y., Fowler, K. E., Wolf, G. T., & Teknos, T. N. (2008) · Cancer · doi:10.1002/cncr.23615 · Cited by 330 · see citing works
Ogino, S., Kawasaki, T., Nosho, K., Ohnishi, M., Suemoto, Y., Kirkner, G. J., & Fuchs, C. S. (2008) · International Journal of Cancer · doi:10.1002/ijc.23470 · Cited by 261 · 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
Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide.
Schwarz, M. A., Lazo, J. S., Yalowich, J. C., Allen, W. P., Whitmore, M., Bergonia, H. A., Tzeng, E., Billiar, T., Robbins, P. D., & Lancaster, J. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4452 · Cited by 244 · see citing works
Wehbe, H., Henson, R., Meng, F., Mize-Berge, J., & Patel, T. C. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-2130 · Cited by 224 · 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
Exploring the link between microorganisms and oral cancer: A systematic review of the literature
Hooper, S. J., Wilson, M. J., & Crean, S. J. (2009) · Head & Neck · doi:10.1002/hed.21140 · Cited by 203 · see citing works
Kristensen, L. S., Mikeska, T., Krypuy, M., & Dobrovic, A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn113 · Cited by 185 · see citing works
Patel, S., Kumar, S., Jyoti, A., Srinag, B. S., Keshari, R. S., Saluja, R., Verma, A. R., Mitra, K., Barthwal, M. K., Krishnamurthy, H., et al. (2010) · Nitric Oxide · doi:10.1016/j.niox.2010.01.001 · Cited by 163 · see citing works
Shinriki, S., Jono, H., Ota, K., Ueda, M., Kudo, M., Ota, T., Oike, Y., Endo, M., Ibusuki, M., Hiraki, A., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0287 · Cited by 163 · see citing works
Foran, E., Garrity-Park, M. M., Mureau, C., Newell, J., Smyrk, T. C., Limburg, P. J., & Egan, L. J. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0496 · Cited by 155 · see citing works
Hodge, D. R., Xiao, W., Clausen, P. A., Heidecker, G., Moshe Szyf, A., & Farrar, W. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100343200 · Cited by 154 · see citing works
Oxidation of elongation factor G inhibits the synthesis of the D1 protein of photosystem II
Kojima, K., Oshita, M., Nanjo, Y., Kasai, K., Tozawa, Y., Hayashi, H., & Nishiyama, Y. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05836.x · Cited by 152 · see citing works
Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer
Choi, S. H., Worswick, S., Byun, H., Shear, T., Soussa, J. C., Wolff, E. M., Douer, D., Garcia‐Manero, G., Liang, G., & Yang, A. S. (2009) · International Journal of Cancer · doi:10.1002/ijc.24384 · Cited by 147 · see citing works
Figueiredo, J. C., Grau, M. V., Wallace, K., Levine, A. J., Shen, L., Hamdan, R., Chen, X., Bresalier, R. S., McKeown‐Eyssen, G., Haile, R. W., et al. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0926 · Cited by 146 · see citing works
Fukushima, N., Sato, N., Sahin, F., Su, G. H., Hruban, R. H., & Goggins, M. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601039 · Cited by 132 · see citing works
Chakravarti, N., Myers, J. N., & Aggarwal, B. B. (2006) · International Journal of Cancer · doi:10.1002/ijc.21967 · Cited by 114 · see citing works
Methylation Array Analysis of Preoperative and Postoperative Saliva DNA in Oral Cancer Patients
Viet, C. T., & Schmidt, B. L. (2008) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0507 · Cited by 114 · see citing works
Shintani, S., Nakahara, Y., Mihara, M., Ueyama, Y., & Matsumura, T. (2001) · Oral Oncology · doi:10.1016/s1368-8375(00)00142-1 · Cited by 111 · see citing works
The epigenetics of oral cancer
Shaw, R. (2005) · International Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.ijom.2005.06.014 · Cited by 107 · see citing works
Goel, A., Xicola, R. M., Nguyen, T., Doyle, B. J., Sohn, V. R., Bandipalliam, P., Rozek, L. S., Reyes, J., Cordero, C., Balaguer, F., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.035 · Cited by 102 · see citing works
Self-citationSalivary concentration of TNFalpha, IL1 alpha, IL6, and IL8 in oral squamous cell carcinoma.
Sahebjamee, M., Eslami, M., Moghadam, F. A., & Sarafnejad, A. (2008) · PubMed · Cited by 100 · see citing works
Comparison of Salivary Cytokine Levels in Oral Cancer Patients and Healthy Subjects
Katakura, A., Kamiyama, I., Takano, N., Shibahara, T., Muramatsu, T., Ishihara, K., Takagi, R., & Shouno, T. (2007) · The Bulletin of Tokyo Dental College · doi:10.2209/tdcpublication.48.199 · Cited by 96 · see citing works
Kayamori, K., Sakamoto, K., Nakashima, T., Takayanagi, H., Morita, K., Omura, K., Nguyen, S. T., Miki, Y., Iimura, T., Himeno, A., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090299 · Cited by 81 · see citing works
Sharma, M., Bairy, I., Pai, K. M., Satyamoorthy, K., Prasad, S., Berkovitz, B. K. B., & Radhakrishnan, R. A. (2010) · Clinical Oral Investigations · doi:10.1007/s00784-010-0435-5 · Cited by 74 · see citing works
Campregher, C., Luciani, M. G., & Gasché, C. (2008) · Gut · doi:10.1136/gut.2007.141556 · Cited by 73 · see citing works
Vairaktaris, E. G., Yapijakis, C., Serefoglou, Z., Avgoustidis, D., Critselis, E., Spyridonidou, S., Vylliotis, A., Derka, S., Vassiliou, S., Nkenke, E., et al. (2008) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-008-0360-z · Cited by 69 · see citing works
Wang, Y., Chang, S., Tai, S., Li, W.-Y., & Wang, L. (2002) · Head & Neck · doi:10.1002/hed.10145 · Cited by 66 · see citing works
Chromosomal Instability in Oral Cancer Cells
Reshmi, S. C., & Gollin, S. M. (2005) · Journal of Dental Research · doi:10.1177/154405910508400203 · Cited by 62 · see citing works
Kim, B., Cho, N., Shin, S. H., Kwon, H.-J., Jang, J. J., & Kang, G. H. (2009) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-009-0829-4 · Cited by 55 · see citing works
Detection of p16 promoter methylation in the serum of oral cancer patients
Nakahara, Y., Shintani, S., Mihara, M., Hino, S., & Hamakawa, H. (2005) · International Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.ijom.2005.08.005 · Cited by 51 · see citing works
Detection of LINE-1s hypomethylation in oral rinses of oral squamous cell carcinoma patients
Subbalekha, K., Pimkhaokham, A., Pavasant, P., Chindavijak, S., Phokaew, C., Shuangshoti, S., Matangkasombut, O., & Mutirangura, A. (2008) · Oral Oncology · doi:10.1016/j.oraloncology.2008.05.002 · Cited by 48 · see citing works
Spindle assembly checkpoint and centrosome abnormalities in oral cancer
Thirthagiri, E., Robinson, M., Huntley, S. P., Davies, M., Yap, L. F., Prime, S. S., & Paterson, I. C. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.09.008 · Cited by 36 · see citing works
de Oliveira, M. V. M., Fraga, C. A. D. C., Gomez, R. S., & de Paula, A. M. B. (2009) · Head & Neck · doi:10.1002/hed.21121 · Cited by 25 · see citing works
Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas
Hara (2009) · Oncology Reports · doi:10.3892/or_00000552 · Cited by 19 · see citing works
Muthusamy, V., Gurunathan, S., Vinod, S. S., Mohanprasad, B. K., & Shanmugam, G. (2003) · PubMed · Cited by 19 · see citing works
Sassano, P., Paparo, F., Ramieri, V., Colangeli, W., & Verdino, G. G. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2006.06.057 · Cited by 5 · see citing works
Flagged first, then by citations
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Sorted by citations
Chronic inflammation and cytokines in the tumor microenvironment
Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C., & Hermoso, M. A. (2014) · Journal of Immunology Research · doi:10.1155/2014/149185 · Cited by 1,765 · see citing works
Role of interleukin-6 in cancer progression and therapeutic resistance
Kumari, N., Dwarakanath, B. S. R., Das, A., & Bhatt, A. N. (2016) · Tumor Biology · doi:10.1007/s13277-016-5098-7 · Cited by 1,096 · 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).”
BackgroundImmunosuppression associated with chronic inflammation in the tumor microenvironment
Wang, D., & DuBois, R. N. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv123 · Cited by 358 · see citing works
Effect of Stromal Cells in Tumor Microenvironment on Metastasis Initiation
Guo, S., & Deng, C. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.25720 · Cited by 320 · see citing works
Interplay between inflammation and cancer
Khandia, R., & Munjal, A. K. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.09.004 · Cited by 292 · see citing works
IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis
Browning, L., Patel, M., Horvath, E. B., Tawara, K., & Jorcyk, C. L. (2018) · Cancer Management and Research · doi:10.2147/cmar.s179189 · Cited by 289 · 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
The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities
Rašková, M., Lacina, L., Kejík, Z., Venhauerova, A., Skaličková, M., Kolář, M., Jakubek, M., Rösel, D., Smetana, K., & Brábek, J. (2022) · Cells · doi:10.3390/cells11223698 · Cited by 234 · see citing works
STAT3 in the Systemic Inflammation of Cancer Cachexia
Zimmers, T., Fishel, M., & Bonetto, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.009 · Cited by 216 · see citing works
Wong, C. P., Rinaldi, N. A., & Ho, E. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400761 · Cited by 174 · see citing works
Interleukin‐6 in oral diseases: a review
Nibali, L., Fedele, S., D’Aiuto, F., & Donos, N. (2011) · Oral Diseases · doi:10.1111/j.1601-0825.2011.01867.x · Cited by 172 · see citing works
Hao, Z., Pan, Y., Shao, W., Lin, Q., & Zhao, X. (2019) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2019.03.053 · Cited by 169 · see citing works
Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature
Mohan, C. D., Rangappa, S., Preetham, H. D., Nayaka, S. C., Gupta, V. K., Basappa, B., Sethi, G., & Rangappa, K. S. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.03.016 · Cited by 158 · see citing works
Xia, X., Wu, W. K. K., Wong, S. H., Liu, D., Kwong, T. N. Y., Nakatsu, G., Yan, P. S., Chuang, Y., Chan, M. W. Y., Coker, O. O., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00847-4 · Cited by 153 · see citing works
The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Moresi, V., Adamo, S., & Berghella, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00500 · Cited by 141 · see citing works
Epigenetic Mechanisms in Oral Carcinogenesis
Gasche, J. A. K., & Goel, A. (2012) · Future Oncology · doi:10.2217/fon.12.138 · Cited by 130 · see citing works
Self-citationPrenatal maternal immune activation causes epigenetic differences in adolescent mouse brain
Basil, P., Li, Q., Dempster, E. L., Mill, J., Sham, P.-C., Wong, C. C. Y., & McAlonan, G. M. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.80 · Cited by 116 · see citing works
LINE-1 in cancer: multifaceted functions and potential clinical implications
Lu, X., Hui-Ying, X., Qi, X., Jiang, X., & Ma, S. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.119 · Cited by 121 · see citing works
From obesity to cancer: a review on proposed mechanisms
Tahergorabi, Z., Khazaei, M., Moodi, M., & Chamani, E. (2016) · Cell Biochemistry and Function · doi:10.1002/cbf.3229 · Cited by 118 · see citing works
Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy
Zhang, Q., Zhu, B., & Li, Y. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00071 · Cited by 118 · see citing works
IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells
Wang, Y., Zong, X., Mitra, S., Mitra, A. K., Matei, D. E., & Nephew, K. P. (2018) · JCI Insight · doi:10.1172/jci.insight.122360 · Cited by 115 · see citing works
IL-6 Activities in the Tumour Microenvironment. Part 1
Chonov, D. C., Ignatova, M., Ananiev, J. R., & Gulubova, M. V. (2019) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2019.589 · Cited by 115 · see citing works
The Role of Inflammation in Head and Neck Cancer
Bonomi, M. R., Patsias, A., Posner, M. R., & Sikora, A. G. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_5 · Cited by 114 · see citing works
Early-Life Stress and Adult Inflammation
Fagundes, C. P., & Way, B. M. (2014) · Current Directions in Psychological Science · doi:10.1177/0963721414535603 · Cited by 113 · see citing works
Hao, Z., Wang, Z., Li, Y., Zhu, Y., Wang, X., Moraes, C. G. D., Pan, Y., Zhao, X., & Lin, Q. (2018) · Nanoscale · doi:10.1039/c8nr04315a · Cited by 105 · see citing works
Tekpli, X., Landvik, N. E., Anmarkud, K. H., Skaug, V., Haugen, A., & Zienolddiny, S. (2012) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-012-1340-3 · Cited by 100 · see citing works
The epigenetic alterations of endogenous retroelements in aging
Cardelli, M. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.02.002 · Cited by 91 · see citing works
Zhang, F. F., Santella, R. M., Wolff, M. S., Deyssenroth, M. A., Markowitz, S. B., & Morabia, A. (2012) · Epigenetics · doi:10.4161/epi.20236 · Cited by 91 · see citing works
Oxidative Stress and Epigenetic Instability in Human Hepatocarcinogenesis
Nishida, N., & Kudo, M. (2013) · Digestive Diseases · doi:10.1159/000355243 · Cited by 91 · see citing works
Ferraguti, G., Terracina, S. A., Petrella, C., Greco, A., Minni, A., Lucarelli, M., Agostinelli, E., Ralli, M., VINCENTIIS, M. D., Raponi, G., et al. (2022) · Antioxidants · doi:10.3390/antiox11010145 · Cited by 90 · see citing works
Huang, L., Hu, B., Ni, J., Wu, J., Jiang, W., Chen, C., Yang, L., Zeng, Y., Wan, R., Hu, G., et al. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0301-7 · Cited by 86 · see citing works
RetractedMarkopoulos, G. S., Roupakia, E., Marcu, K. B., & Kolettas, E. (2019) · Cells · doi:10.3390/cells8101143 · Cited by 83 · see citing works
Exploring the Crosstalk between Inflammation and Epithelial‐Mesenchymal Transition in Cancer
Chattopadhyay, I., Ambati, R. R., & Gundamaraju, R. (2021) · Mediators of Inflammation · doi:10.1155/2021/9918379 · Cited by 81 · see citing works
Mechanisms and Αpplications of Ιnterleukins in Cancer Immunotherapy
Anestakis, D., Petanidis, S., Kalyvas, S., Nday, C. M., Tsave, O., Kioseoglou, E., & Salifoglou, A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16011691 · Cited by 79 · see citing works
Epigenetic Regulation of Inflammatory Signaling and Inflammation-Induced Cancer
Tan, S. Y. X., Zhang, J., & Tee, W. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.931493 · Cited by 83 · see citing works
Kawano, H., Saeki, H., Kitao, H., Tsuda, Y., Otsu, H., Ando, K., Ito, S., Egashira, A., Oki, E., Morita, M., et al. (2014) · Annals of Surgical Oncology · doi:10.1245/s10434-014-3818-z · Cited by 76 · see citing works
Roy, S., Glaser, S. S., & Chakraborty, S. (2019) · Frontiers in Medicine · doi:10.3389/fmed.2019.00293 · Cited by 72 · see citing works
Interleukin-6 role in head and neck squamous cell carcinoma progression
Choudhary, M. M., France, T., Teknos, T., & Kumar, P. (2016) · World Journal of Otorhinolaryngology-Head and Neck Surgery · doi:10.1016/j.wjorl.2016.05.002 · Cited by 67 · see citing works
Khosravi, F., Loeian, M. S., & Panchapakesan, B. (2017) · Biosensors · doi:10.3390/bios7020017 · Cited by 71 · see citing works
Microbial and inflammatory‐based salivary biomarkers of head and neck squamous cell carcinoma
Vesty, A., Gear, K., Biswas, K., Radcliff, F. J., Taylor, M. W., & Douglas, R. G. (2018) · Clinical and Experimental Dental Research · doi:10.1002/cre2.139 · Cited by 71 · see citing works
Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review
Mesgari, H., Esmaelian, S., Nasiri, K., Ghasemzadeh, S., Doroudgar, P., & Payandeh, Z. (2023) · Cancers · doi:10.3390/cancers15235600 · Cited by 81 · see citing works
Che, Q., Liu, B., Liao, Y. J., Zhang, H., Yang, T., He, Y., Xia, Y., Lu, W., He, X., Chen, Z., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28679 · Cited by 69 · see citing works
Wang, L., Yin, P., Wang, J., Wang, Y., Sun, Z., Zhou, Y., & Guan, X. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1623232 · Cited by 62 · see citing works
Mirzaei, S., Gholami, M., Mahabady, M. K., Nabavi, N., Zabolian, A., Banihashemi, S. M., Haddadi, A., Entezari, M., Hushmandi, K., Makvandi, P., et al. (2021) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2020.111077 · Cited by 59 · see citing works
RetractedBurris, H. H., Rifas‐Shiman, S. L., Baccarelli, A., Tarantini, L., Boeke, C. E., KLEINMAN, K. P., Litonjua, A. A., Rich-Edwards, J. W., & Gillman, M. W. (2012) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174412000104 · Cited by 61 · see citing works
Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy
Cruickshank, B. M., Giacomantonio, M., Marcato, P., McFarland, S. A., Pol, J. G., & Gujar, S. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00654 · Cited by 61 · see citing works
Pacaud, R., Brocard, E., Lalier-Bretaudeau, L., Hervouet, É., Vallette, F. M., & Cartron, P. (2014) · Scientific Reports · doi:10.1038/srep04230 · Cited by 59 · see citing works
Anti-inflammatory and anti-aging effects of hydroxytyrosol on human dermal fibroblasts (HDFs)
Jeon, S., & Choi, M. (2018) · Biomedical Dermatology · doi:10.1186/s41702-018-0031-x · Cited by 57 · see citing works
Wu, J., Xu, Y., Mo, D., Huang, P., Sun, R., Huang, L., Pan, S., & Xu, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093478 · Cited by 54 · see citing works
Nardini, C., Moreau, J., Gensous, N., Ravaioli, F., Garagnani, P., & Bacalini, M. G. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.10.009 · Cited by 54 · see citing works
Crosstalk Between Inflammatory Signaling and Methylation in Cancer
Das, D., Karthik, N., & Taneja, R. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.756458 · Cited by 54 · see citing works
The influence of epigenetics in relation to oral health
Lod, S., Johansson, T., Abrahamsson, K., & Larsson, L. (2013) · International Journal of Dental Hygiene · doi:10.1111/idh.12030 · Cited by 52 · see citing works
Wongpaiboonwattana, W., Tosukhowong, P., Dissayabutra, T., Mutirangura, A., & Boonla, C. (2013) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2013.14.6.3773 · Cited by 52 · see citing works
Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies
de Wit, S., Glen, C., de Boer, R. A., & Lang, N. N. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac132 · Cited by 52 · see citing works
Clinical implications of epigenetic regulation in oral cancer
D’Souza, W., & Saranath, D. (2015) · Oral Oncology · doi:10.1016/j.oraloncology.2015.09.006 · Cited by 50 · see citing works
Animal Models of Maternal Immune Activation in Depression Research
Ronovsky, M., Berger, S., Molz, B., Berger, A., & Pollak, D. D. (2015) · Current Neuropharmacology · doi:10.2174/1570159x14666151215095359 · Cited by 49 · see citing works
Flausino, C. S., Daniel, F. I., & Modolo, F. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103399 · Cited by 47 · see citing works
Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers
Ni, Y., Low, J. T., Silke, J., & O’Reilly, L. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.835997 · Cited by 46 · see citing works
DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma
Huang, Y., Peng, B., Wu, C.-Y., Su, C., Wang, H.-C., & Lai, H. (2013) · Clinical Oral Investigations · doi:10.1007/s00784-013-1048-6 · Cited by 46 · see citing works
Nerve Growth Factor and the Role of Inflammation in Tumor Development
Ferraguti, G., Terracina, S. A., Tarani, L., Fanfarillo, F., Allushi, S., Caronti, B., Tirassa, P., Polimeni, A., Lucarelli, M., Cavalcanti, L., et al. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46020062 · Cited by 45 · see citing works
Basil, P., Li, Q., Gui, H., Hui, T. C. K., Ling, V. H. M., Wong, C. C. Y., Mill, J. S., McAlonan, G. M., & Sham, P. C. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0167-x · Cited by 45 · see citing works
Pundir, M., Papagerakis, S. M., Rosa, M. C. D., Chronis, N., Kurabayashi, K., Abdulmawjood, S., Prince, M. E. P., Lobanova, L., Chen, D., & Papagerakis, P. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.107961 · Cited by 44 · see citing works
The Role of Epigenomics in the Study of Cancer Biomarkers and in the Development of Diagnostic Tools
Verma, M. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-7215-0_5 · Cited by 44 · see citing works
Zhang, J., Zhang, H., Ding, X., Hu, J., Li, Y., Zhang, J., Wang, H., Qi, S., Xie, A., Shi, J., et al. (2022) · Theranostics · doi:10.7150/thno.69494 · Cited by 43 · see citing works
Rey, E. O., Suárez‐Alén, F., Mallón, M. P., López‐López, J., & Carrión, A. B. (2014) · Acta Odontologica Scandinavica · doi:10.3109/00016357.2014.914570 · Cited by 43 · see citing works
Tumor-like microenvironment in oral lichen planus: evidence of malignant transformation?
Peng, Q., Zhang, J., Ye, X., & Zhou, G. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1295852 · Cited by 43 · see citing works
Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review
Uz, U., & Eskiizmir, G. (2021) · Clinical and Experimental Otorhinolaryngology · doi:10.21053/ceo.2019.00906 · Cited by 43 · see citing works
Biomarkers of head and neck cancer, tools or a gordian knot?
Lampri, E. S., Chondrogiannis, G., Ioachim, E. E., Varouktsi, A., Mitselou, A., Galani, A., Briassoulis, E., Kanavaros, P., & Galani, V. (2015) · PubMed Central · Cited by 42 · see citing works
Gender Difference in the Prognostic Role of Interleukin 6 in Oral Squamous Cell Carcinoma
Chen, C.-J., Sung, W., Lin, Y.-M., Chen, M. K., Lee, C.-H., Lee, H., Yeh, K.-T., & Ko, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050104 · Cited by 39 · see citing works
Pitaksalee, R., Burska, A., Ajaib, S., Rogers, J. H., Parmar, R., Mydlova, K., Xie, X., Droop, A., Nijjar, J. S., Chambers, P. A., et al. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00837-1 · Cited by 37 · see citing works
Oxidative Stress and Inflammation Can Fuel Cancer
Vaidya, F. U., Chhipa, A. S., Sagar, N., & Pathak, C. (2020) · Springer eBooks · doi:10.1007/978-981-15-1568-2_14 · Cited by 37 · see citing works
Harun-Or-Roshid, M., Ali, M. B., Jesmin, J., & Mollah, M. N. H. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247055 · Cited by 37 · see citing works
Zhu, J., Guo, B., Fu, M., Guo, W., Yuan, Y., Yuan, H., Zhang, S., & Yu, H. (2016) · Disease Markers · doi:10.1155/2016/9612421 · Cited by 36 · see citing works
Significance of DNMT3b in Oral Cancer
Chen, W., Chen, M., & Lin, P.-Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089956 · Cited by 35 · see citing works
Notley, C. A., Jordan, C. K. I., McGovern, J. L., Brown, M. A., & Ehrenstein, M. R. (2017) · Scientific Reports · doi:10.1038/srep42204 · Cited by 35 · see citing works
Tanıs, T., Çinçin, Z. B., Röhli̇g, B. G., Bireller, E. S., Ulusan, M., Tanyel, C., & Çakmakoğlu, B. (2014) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2014.07.005 · Cited by 35 · see citing works
High-Resolution Array CGH and Gene Expression Profiling of Alveolar Soft Part Sarcoma
Selvarajah, S., Pyne, S., Chen, E. Y., Sompallae, R. R., Ligon, A. H., Nielsen, G. P., Dranoff, G., Stack, E. C., Loda, M. F., & Flavin, R. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2090 · Cited by 35 · see citing works
Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View
Nenu, I., Toadere, T. M., Topor, I., Țichindeleanu, A., Bondor, D. A., Trella, Ș. E., Sparchez, Z. A., & Filip, G. A. (2023) · Biomedicines · doi:10.3390/biomedicines11102623 · Cited by 34 · see citing works
Yáñez, L., Soto, C., Tapia, H., Pacheco, M., Tapia, J., Osses, G., Salinas, D., Rojas-Celis, V., Hoare, A., Quest, A. F. G., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073611 · Cited by 34 · see citing works
Periodontal Pathogens: A Crucial Link Between Periodontal Diseases and Oral Cancer
Li, T., Hao, Y., Tang, Y., & Liang, X. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.919633 · Cited by 34 · see citing works
Barros, S. P., Fahimipour, F., Tarran, R., Kim, S., Scarel‐Caminaga, R. M., Justice, A. E., & North, K. E. (2019) · Periodontology 2000 · doi:10.1111/prd.12322 · Cited by 30 · see citing works
Almeida, L. O., Neto, M. P. C., Sousa, L. O., Tannous, M. A., Curti, C., & Leopoldino, A. M. (2017) · Oncotarget · doi:10.18632/oncotarget.15818 · Cited by 28 · see citing works
Wang, C., O’Brien, K. M., Xu, Z., Sandler, D. P., Taylor, J. A., & Weinberg, C. R. (2019) · Epigenetics · doi:10.1080/15592294.2019.1699894 · Cited by 29 · see citing works
Genome-wide analysis of DNA methylation in UVB- and DMBA/TPA-induced mouse skin cancer models
Yang, Y., Lee, J. H., Shu, L., Zhang, C., Su, Z., Lu, Y.-P., Huang, M., Ramirez, C. N., Pung, D., Huang, Y. S., et al. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.07.031 · Cited by 29 · see citing works
Kabza, M., Karolak, J. A., Rydzanicz, M., Udziela, M., Gasperowicz, P., Płoski, R., Szaflik, J. P., & Gajęcka, M. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25916 · Cited by 28 · see citing works
Johnston, P. A., Sen, M., Hua, Y., Camarco, D. P., Shun, T. Y., Lazo, J. S., Wilson, G. M., Resnick, L., LaPorte, M. G., Wipf, P., et al. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.663 · Cited by 27 · see citing works
Liu, P., Zhou, T., Qiu, B.-A., Yang, Y., Zhu, Y., An, Y., Zhao, W., Wu, Y., Ma, P., Li, J., et al. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.01.023 · Cited by 27 · see citing works
Chen, Y., Chen, F. Y. T., Vijmasi, T., Stephens, D. N., Gallup, M., & McNamara, N. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077286 · Cited by 27 · see citing works
Sinkovics, J. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1248 · Cited by 27 · see citing works
Tuberculous Fibrosis Enhances Tumorigenic Potential via the NOX4–Autophagy Axis
Woo, S. J., Kim, Y., Jung, H., Lee, J. J., & Hong, J. Y. (2021) · Cancers · doi:10.3390/cancers13040687 · Cited by 24 · see citing works
Kaur, J., Preethi, M., Srivastava, R., & Borse, V. B. (2022) · Biosensors and Bioelectronics X · doi:10.1016/j.biosx.2022.100212 · Cited by 24 · see citing works
Singh, R. K. (2011) · Journal of Cancer Science & Therapy · doi:10.4172/1948-5956.1000061 · Cited by 24 · see citing works
Piskareva, O., Lackington, W. A., Lemass, D., Hendrick, C. A., Doolan, P., & Barron, N. (2011) · Current Molecular Medicine · doi:10.2174/156652411795677954 · Cited by 23 · see citing works
Methylation-Mediated Molecular Dysregulation in Clinical Oral Malignancy
Towle, R. M., & Garnis, C. (2012) · Journal of Oncology · doi:10.1155/2012/170172 · Cited by 22 · see citing works
Reproducibility and Concordance of Differential DNA Methylation and Gene Expression in Cancer
Yao, C., Li, H., Shen, X., He, Z., He, L. C., & Guo, Z. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029686 · Cited by 22 · see citing works
Cheng, C.-P., Kuo, I., Alakus, H., Frazer, K. A., Harismendy, O., Wang, Y., & Tseng, V. S. M. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu433 · Cited by 22 · see citing works
Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma
Yong-Deok, K., Eun-Hyoung, J., Yeon-Sun, K., Mi, P. K., Jin-Yong, L., Sung-Hwan, C., Tae-Yun, K., Tae-Sung, P., Soung-Min, K., Myung-Jin, K., et al. (2014) · Medicina oral, patología oral y cirugía bucal · doi:10.4317/medoral.20229 · Cited by 22 · see citing works
Ding, X., Li, F., & Zhang, L. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.04.024 · Cited by 22 · see citing works
Interleukin-6 as a therapy target in oral squamous carcinoma
Čulig, Z. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.733368 · Cited by 21 · see citing works
- Authors
- Gasche, J. A., Hoffmann, J., Boland, C. R., & Goel, A.
- Affiliations
- Baylor University Medical Center (US)
- University Hospital Heidelberg (DE)
- Corresponding author
- Boland, C. Richard
- Goel, Ajay
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2011-01-07
- Volume
- 129
- Issue
- 5
- Pages
- 1053-1063
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- PMC
- PMC3110561
- OpenAlex
- W2006992975
- Cited by
- 178
- References
- 51
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 7 · 2023: 10 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 15 · 2018: 18 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 15 · 2013: 9 · 2012: 15
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Texas A and M University
- University of Pittsburgh
- Universität Wien
- National Institutes of Health
- National Cancer Institute (R01-CA-72851, CA72851, R01CA072851, R01CA129286, CA129286)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
- Keywords
- interleukin-6, oral squamous cell carcinoma, DNA methylation, LINE-1 hypomethylation, chronic inflammation, tumor suppressor, promoter hypermethylation, epigenetic silencing, CHFR, GATA5, Pax6, carcinogenesis
- MeSH terms
- Carcinoma, Squamous Cell, DNA, Neoplasm, Humans, Inflammation, Mouth Neoplasms, Phosphorylation, Promoter Regions, Genetic, RNA, Messenger, Tumor Cells, Cultured, Interleukin-6, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, Genes, Tumor Suppressor, CpG Islands, DNA Methylation, Long Interspersed Nucleotide Elements, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Epigenomics
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