{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:47:38Z","timestamp":1782107258564,"version":"3.54.5"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"the Natural Science Foundation of Liaoning Province","award":["No.2023-MS-262"],"award-info":[{"award-number":["No.2023-MS-262"]}]},{"DOI":"10.13039\/501100010018","name":"Doctoral Start-up Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["No. LJKMZ20221276"],"award-info":[{"award-number":["No. LJKMZ20221276"]}],"id":[{"id":"10.13039\/501100010018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Biochem Biotechnol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s12010-026-05691-0","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:35:06Z","timestamp":1776144906000},"page":"5166-5191","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Tumor-Promoting Role of ADM in Bladder Cancer and its Mediated Mechanisms of Cell Death via PKR and STAT1"],"prefix":"10.1007","volume":"198","author":[{"given":"Xiaowen","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"issue":"3","key":"5691_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. C Ca: A Cancer Journal For Clinicians, 74(3), 229\u2013263.","journal-title":"C Ca: A Cancer Journal For Clinicians"},{"issue":"1","key":"5691_CR2","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. C Ca: A Cancer Journal For Clinicians, 73(1), 17\u201348.","journal-title":"C Ca: A Cancer Journal For Clinicians"},{"issue":"1","key":"5691_CR3","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.eururo.2016.02.028","volume":"70","author":"PA Humphrey","year":"2016","unstructured":"Humphrey, P. A., Moch, H., Cubilla, A. L., Ulbright, T. M., & Reuter, V. E. (2016). The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. European Urology, 70(1), 106\u2013119.","journal-title":"European Urology"},{"issue":"0 23","key":"5691_CR4","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.1002\/cncr.29047","volume":"120","author":"ME Charlton","year":"2014","unstructured":"Charlton, M. E., Adamo, M. P., Sun, L., & Deorah, S. (2014). Bladder cancer collaborative stage variables and their data quality, usage, and clinical implications: a review of SEER data, 2004\u20132010. Cancer, 120(0 23), 3815\u20133825.","journal-title":"Cancer"},{"issue":"3","key":"5691_CR5","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.eururo.2006.04.005","volume":"50","author":"M Maffezzini","year":"2006","unstructured":"Maffezzini, M. (2006). Re: Richard J. Sylvester, Adrian P.M., van der Meijden, Willem, Oosterlinck, J. Alfred, Witjes, Christian, & Bouffioux, Louis Denis and Donald W.W. Newling. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49:466\u2009\u2013\u200977. European Urology, 50(3), 623\u2013624. 624\u2009\u2013\u2009625.","journal-title":"European Urology"},{"issue":"2","key":"5691_CR6","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1111\/bju.14872","volume":"125","author":"A Martini","year":"2020","unstructured":"Martini, A., Sfakianos, J. P., Renstrom-Koskela, L., Mortezavi, A., Falagario, U. G., Egevad, L., Hosseini, A., Mehrazin, R., Galsky, M. D., Steineck, G., & Wiklund, N. P. (2020). The natural history of untreated muscle-invasive bladder cancer. Bju International, 125(2), 270\u2013275.","journal-title":"Bju International"},{"issue":"3","key":"5691_CR7","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.bbrc.2012.08.022","volume":"425","author":"K Kitamura","year":"2012","unstructured":"Kitamura, K., Kangawa, K., Kawamoto, M., Ichiki, Y., Nakamura, S., Matsuo, H., & Eto, T. (2012). Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. 1993. Biochemical And Biophysical Research Communications, 425(3), 548\u2013555.","journal-title":"Biochemical And Biophysical Research Communications"},{"key":"5691_CR8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.peptides.2018.03.012","volume":"111","author":"T Tsuruda","year":"2019","unstructured":"Tsuruda, T., Kato, J., Kuwasako, K., & Kitamura, K. (2019). Adrenomedullin: Continuing to explore cardioprotection. Peptides, 111, 47\u201354.","journal-title":"Peptides"},{"issue":"2","key":"5691_CR9","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/ejhf.1366","volume":"21","author":"AA Voors","year":"2019","unstructured":"Voors, A. A., Kremer, D., Geven, C., Ter Maaten, J. M., Struck, J., Bergmann, A., Pickkers, P., Metra, M., Mebazaa, A., Dungen, H. D., & Butler, J. (2019). Adrenomedullin in heart failure: pathophysiology and therapeutic application. European Journal Of Heart Failure, 21(2), 163\u2013171.","journal-title":"European Journal Of Heart Failure"},{"issue":"5","key":"5691_CR10","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.3892\/etm.2015.2345","volume":"9","author":"W Hu","year":"2015","unstructured":"Hu, W., Zhou, P. H., Zhang, X. B., Xu, C. G., & Wang, W. (2015). Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension. Exp Ther Med, 9(5), 1901\u20131908.","journal-title":"Exp Ther Med"},{"key":"5691_CR11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jcrc.2016.10.017","volume":"38","author":"TP Simon","year":"2017","unstructured":"Simon, T. P., Martin, L., Doemming, S., Humbs, A., Bruells, C., Kopp, R., Hartmann, O., Struck, J., Bergmann, A., Marx, G., & Schuerholz, T. (2017). Plasma adrenomedullin in critically ill patients with sepsis after major surgery: A pilot study. Journal Of Critical Care, 38, 68\u201372.","journal-title":"Journal Of Critical Care"},{"issue":"51","key":"5691_CR12","doi-asserted-by":"publisher","first-page":"88464","DOI":"10.18632\/oncotarget.18881","volume":"8","author":"F Qiao","year":"2017","unstructured":"Qiao, F., Fang, J., Xu, J., Zhao, W., Ni, Y., Akuo, B. A., Zhang, W., Liu, Y., Ding, F., Li, G., Liu, B., Wang, H., & Shao, S. (2017). The role of adrenomedullin in the pathogenesis of gastric cancer. Oncotarget, 8(51), 88464\u201388474.","journal-title":"Oncotarget"},{"issue":"3","key":"5691_CR13","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.3892\/mmr.2014.2320","volume":"10","author":"F Li","year":"2014","unstructured":"Li, F., Yang, R., Zhang, X., Liu, A., Zhao, Y., & Guo, Y. (2014). Silencing of hypoxia\u2013inducible adrenomedullin using RNA interference attenuates hepatocellular carcinoma cell growth in vivo. Molecular Medicine Reports, 10(3), 1295\u20131302.","journal-title":"Molecular Medicine Reports"},{"issue":"2","key":"5691_CR14","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3892\/ol.2015.3278","volume":"10","author":"M Li","year":"2015","unstructured":"Li, M., Hong, L. I., Liao, M., & Guo, G. (2015). Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer. Oncol Lett, 10(2), 1003\u20131007.","journal-title":"Oncol Lett"},{"issue":"5","key":"5691_CR15","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3892\/mmr.2012.1045","volume":"6","author":"JY Kim","year":"2012","unstructured":"Kim, J. Y., Park, W. D., Lee, S., & Park, J. H. (2012). Adrenomedullin is involved in the progression of colonic adenocarcinoma. Molecular Medicine Reports, 6(5), 1030\u20131034.","journal-title":"Molecular Medicine Reports"},{"issue":"6","key":"5691_CR16","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1053\/j.gastro.2012.08.044","volume":"143","author":"G Aggarwal","year":"2012","unstructured":"Aggarwal, G., Ramachandran, V., Javeed, N., Arumugam, T., Dutta, S., Klee, G. G., Klee, E. W., Smyrk, T. C., Bamlet, W., Han, J. J., Rumie, V. N., de Andrade, M., Mukhopadhyay, D., Petersen, G. M., Fernandez-Zapico, M. E., Logsdon, C. D., & Chari, S. T. (2012). Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in beta cells and mice. Gastroenterology, 143(6), 1510\u20131517.","journal-title":"Gastroenterology"},{"issue":"1","key":"5691_CR17","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s12032-012-0347-0","volume":"30","author":"X Dai","year":"2013","unstructured":"Dai, X., Ma, W., He, X. J., & Jha, R. K. (2013). Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma. Medical Oncology, 30(1), 347.","journal-title":"Medical Oncology"},{"issue":"18","key":"5691_CR18","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.1038\/sj.onc.1205374","volume":"21","author":"MK Oehler","year":"2002","unstructured":"Oehler, M. K., Hague, S., Rees, M. C., & Bicknell, R. (2002). Adrenomedullin promotes formation of xenografted endometrial tumors by stimulation of autocrine growth and angiogenesis. Oncogene, 21(18), 2815\u20132821.","journal-title":"Oncogene"},{"issue":"1\u20133","key":"5691_CR19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.regpep.2005.09.026","volume":"133","author":"I Abasolo","year":"2006","unstructured":"Abasolo, I., Montuenga, L. M., & Calvo, A. (2006). Adrenomedullin prevents apoptosis in prostate cancer cells. Regulatory Peptides, 133(1\u20133), 115\u2013122.","journal-title":"Regulatory Peptides"},{"issue":"10","key":"5691_CR20","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/s41419-018-1100-1","volume":"9","author":"YP Lv","year":"2018","unstructured":"Lv, Y. P., Peng, L. S., Wang, Q. H., Chen, N., Teng, Y. S., Wang, T. T., Mao, F. Y., Zhang, J. Y., Cheng, P., Liu, Y. G., Kong, H., Wu, X. L., Hao, C. J., Chen, W., Zhu, J., Han, B., Ma, Q., Li, K., Zou, Q., & Zhuang, Y. (2018). Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression. Cell Death And Disease, 9(10), 1034.","journal-title":"Cell Death And Disease"},{"key":"5691_CR21","doi-asserted-by":"crossref","unstructured":"Baranello, C., Mariani, M., Andreoli, M., Fanelli, M., Martinelli, E., Ferrandina, G., Scambia, G., Shahabi, S., & Ferlini, C. (2012). Adrenomedullin in ovarian cancer: foe in vitro and friend in vivo? PLoS One, 7(7), e40678.","DOI":"10.1371\/journal.pone.0040678"},{"issue":"3","key":"5691_CR22","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1007\/s12032-013-0616-6","volume":"30","author":"AG Liu","year":"2013","unstructured":"Liu, A. G., Zhang, X. Z., Li, F. B., Zhao, Y. L., Guo, Y. C., & Yang, R. M. (2013). RNA interference targeting adrenomedullin induces apoptosis and reduces the growth of human bladder urothelial cell carcinoma. Medical Oncology, 30(3), 616.","journal-title":"Medical Oncology"},{"key":"5691_CR23","doi-asserted-by":"crossref","unstructured":"Ahn, J. H., Kang, C. K., Kim, E. M., Kim, A. R., & Kim, A. (2022). Proteomics for Early Detection of Non-Muscle-Invasive Bladder Cancer: Clinically Useful Urine Protein Biomarkers. Life (Basel), 12(3), 395.","DOI":"10.3390\/life12030395"},{"key":"5691_CR24","doi-asserted-by":"publisher","first-page":"173041","DOI":"10.1016\/j.ejphar.2020.173041","volume":"876","author":"MM Jia","year":"2020","unstructured":"Jia, M. M., Li, Y. Q., Xu, K. Q., Zhang, Y. Y., Tan, S. M., Zhang, Q., Peng, J., & Luo, X. J. (2020). Jujuboside B promotes the death of acute leukemia cell in a RIPK1\/RIPK3\/MLKL pathway-dependent manner. European Journal Of Pharmacology, 876, 173041.","journal-title":"European Journal Of Pharmacology"},{"key":"5691_CR25","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1126\/sciimmunol.aaw2004","volume":"4","author":"AG Snyder","year":"2019","unstructured":"Snyder, A. G., Hubbard, N. W., Messmer, M. N., Kofman, S. B., Hagan, C. E., Orozco, S. L., Chiang, K., Daniels, B. P., Baker, D., & Oberst, A. (2019). Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity. Sci Immunol, 4, 36.","journal-title":"Sci Immunol"},{"issue":"5","key":"5691_CR26","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","volume":"18","author":"D Bertheloot","year":"2021","unstructured":"Bertheloot, D., Latz, E., & Franklin, B. S. (2021). Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cellular & Molecular Immunology, 18(5), 1106\u20131121.","journal-title":"Cellular & Molecular Immunology"},{"issue":"11\u201312","key":"5691_CR27","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1007\/s00018-016-2190-5","volume":"73","author":"J Zhang","year":"2016","unstructured":"Zhang, J., Yang, Y., He, W., & Sun, L. (2016). Necrosome core machinery: MLKL. Cellular And Molecular Life Sciences, 73(11\u201312), 2153\u20132163.","journal-title":"Cellular And Molecular Life Sciences"},{"key":"5691_CR28","doi-asserted-by":"publisher","first-page":"6184802","DOI":"10.1155\/2022\/6184802","volume":"2022","author":"F Liu","year":"2022","unstructured":"Liu, F., Wei, T., Liu, L., Hou, F., Xu, C., Guo, H., Zhang, W., Ma, M., Zhang, Y., Yu, Q., & Wang, J. (2022). Role of Necroptosis and Immune Infiltration in Human Stanford Type A Aortic Dissection: Novel Insights from Bioinformatics Analyses. Oxid Med Cell Longev, 2022, 6184802.","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"5691_CR29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","volume":"20","author":"J Yuan","year":"2019","unstructured":"Yuan, J., Amin, P., & Ofengeim, D. (2019). Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nature Reviews Neuroscience, 20(1), 19\u201333.","journal-title":"Nature Reviews Neuroscience"},{"key":"5691_CR30","doi-asserted-by":"crossref","unstructured":"Mohammed, S., Thadathil, N., Selvarani, R., Nicklas, E. H., Wang, D., Miller, B. F., Richardson, A., & Deepa, S. S. (2021). Necroptosis contributes to chronic inflammation and fibrosis in aging liver. Aging Cell, 20(12), e13512.","DOI":"10.1111\/acel.13512"},{"issue":"1","key":"5691_CR31","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.trecan.2021.09.003","volume":"8","author":"J Yan","year":"2022","unstructured":"Yan, J., Wan, P., Choksi, S., & Liu, Z. G. (2022). Necroptosis and tumor progression. Trends Cancer, 8(1), 21\u201327.","journal-title":"Trends Cancer"},{"issue":"5","key":"5691_CR32","doi-asserted-by":"publisher","first-page":"7585","DOI":"10.3892\/mmr.2017.7578","volume":"16","author":"TH Kim","year":"2017","unstructured":"Kim, T. H., & Cho, S. G. (2017). Kisspeptin inhibits cancer growth and metastasis via activation of EIF2AK2. Molecular Medicine Reports, 16(5), 7585\u20137590.","journal-title":"Molecular Medicine Reports"},{"issue":"33","key":"5691_CR33","doi-asserted-by":"publisher","first-page":"E3109","DOI":"10.1073\/pnas.1301218110","volume":"110","author":"RJ Thapa","year":"2013","unstructured":"Thapa, R. J., Nogusa, S., Chen, P., Maki, J. L., Lerro, A., Andrake, M., Rall, G. F., Degterev, A., & Balachandran, S. (2013). Interferon-induced RIP1\/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc Natl Acad Sci U S A, 110(33), E3109\u2013E3118.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"5691_CR34","first-page":"409","volume":"72","author":"KD Miller","year":"2022","unstructured":"Miller, K. D., Nogueira, L., Devasia, T., Mariotto, A. B., Yabroff, K. R., Jemal, A., Kramer, J., & Siegel, R. L. (2022). Cancer treatment and survivorship statistics, 2022. C Ca: A Cancer Journal For Clinicians, 72(5), 409\u2013436.","journal-title":"C Ca: A Cancer Journal For Clinicians"},{"issue":"9","key":"5691_CR35","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nrurol.2017.82","volume":"14","author":"N Lobo","year":"2017","unstructured":"Lobo, N., Mount, C., Omar, K., Nair, R., Thurairaja, R., & Khan, M. S. (2017). Landmarks in the treatment of muscle-invasive bladder cancer. Nature Reviews. Urology, 14(9), 565\u2013574.","journal-title":"Nature Reviews. Urology"},{"issue":"5","key":"5691_CR36","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/ijcp.12075","volume":"67","author":"TR Griffiths","year":"2013","unstructured":"Griffiths, T. R. (2013). Current perspectives in bladder cancer management. International Journal Of Clinical Practice, 67(5), 435\u2013448.","journal-title":"International Journal Of Clinical Practice"},{"issue":"2","key":"5691_CR37","first-page":"138","volume":"21","author":"JP Hinson","year":"2000","unstructured":"Hinson, J. P., Kapas, S., & Smith, D. M. (2000). Adrenomedullin, a multifunctional regulatory peptide. Endocrine Reviews, 21(2), 138\u2013167.","journal-title":"Endocrine Reviews"},{"issue":"4","key":"5691_CR38","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1002\/bab.2233","volume":"69","author":"M Asadi","year":"2022","unstructured":"Asadi, M., Taghizadeh, S., Kaviani, E., Vakili, O., Taheri-Anganeh, M., Tahamtan, M., & Savardashtaki, A. (2022). Caspase-3: Structure, function, and biotechnological aspects. Biotechnol Appl Biochem, 69(4), 1633\u20131645.","journal-title":"Biotechnol Appl Biochem"},{"issue":"7","key":"5691_CR39","first-page":"1217","volume":"11","author":"AG Eliopoulos","year":"1995","unstructured":"Eliopoulos, A. G., Kerr, D. J., Herod, J., Hodgkins, L., Krajewski, S., Reed, J. C., & Young, L. S. (1995). The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2. Oncogene, 11(7), 1217\u20131228.","journal-title":"Oncogene"},{"issue":"1","key":"5691_CR40","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","volume":"22","author":"A Glaviano","year":"2023","unstructured":"Glaviano, A., Foo, A., Lam, H. Y., Yap, K., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., Kulke, M. H., Baird, R. D., Prabhu, J. S., Carbone, D., Pecoraro, C., Teh, D., Sethi, G., Cavalieri, V., Lin, K. H., Javidi-Sharifi, N. R., Toska, E., Davids, M. S., Brown, J. R., Diana, P., Stebbing, J., Fruman, D. A., & Kumar, A. P. (2023). PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer. Molecular Cancer, 22(1), 138.","journal-title":"Molecular Cancer"},{"key":"5691_CR41","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.gene.2019.02.076","volume":"698","author":"S Noorolyai","year":"2019","unstructured":"Noorolyai, S., Shajari, N., Baghbani, E., Sadreddini, S., & Baradaran, B. (2019). The relation between PI3K\/AKT signalling pathway and cancer. Gene, 698, 120\u2013128.","journal-title":"Gene"},{"key":"5691_CR42","doi-asserted-by":"publisher","first-page":"7201549","DOI":"10.1155\/2016\/7201549","volume":"2016","author":"PH Zhou","year":"2016","unstructured":"Zhou, P. H., Hu, W., Zhang, X. B., Wang, W., & Zhang, L. J. (2016). Protective Effect of Adrenomedullin on Rat Leydig Cells from Lipopolysaccharide-Induced Inflammation and Apoptosis via the PI3K\/Akt Signaling Pathway ADM on Rat Leydig Cells from Inflammation and Apoptosis. Mediators Inflamm, 2016, 7201549.","journal-title":"Mediators Inflamm"},{"key":"5691_CR43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.semcancer.2019.10.002","volume":"60","author":"Y Verhoeven","year":"2020","unstructured":"Verhoeven, Y., Tilborghs, S., Jacobs, J., De Waele, J., Quatannens, D., Deben, C., Prenen, H., Pauwels, P., Trinh, X. B., Wouters, A., Smits, E., Lardon, F., & van Dam, P. A. (2020). The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol, 60, 41\u201356.","journal-title":"Semin Cancer Biol"},{"key":"5691_CR44","doi-asserted-by":"publisher","first-page":"636595","DOI":"10.3389\/fcell.2021.636595","volume":"9","author":"X Li","year":"2021","unstructured":"Li, X., Wang, F., Xu, X., Zhang, J., & Xu, G. (2021). The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials. Front Cell Dev Biol, 9, 636595.","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"5691_CR45","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.7150\/thno.51245","volume":"11","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Liu, Z., Yang, X., Lu, W., Chen, Y., Lin, Y., Wang, J., Lin, S., & Yun, J. P. (2021). H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. Theranostics, 11(3), 1473\u20131492.","journal-title":"Theranostics"},{"key":"5691_CR46","doi-asserted-by":"publisher","first-page":"109551","DOI":"10.1016\/j.exer.2023.109551","volume":"233","author":"Y Wang","year":"2023","unstructured":"Wang, Y., Hong, Y., Mao, S., Pan, J., Cui, Y., Lu, J., Wen, T., Wang, X., & Luo, Y. (2023). Downregulation of miR-124-3p suppresses the development of the deep retinal blood vessels by enhancing the Stat1\/Ripk1 pathway in mouse retinal microglia. Experimental Eye Research, 233, 109551.","journal-title":"Experimental Eye Research"},{"issue":"1","key":"5691_CR47","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13020-024-00883-4","volume":"19","author":"S Zhang","year":"2024","unstructured":"Zhang, S., Liu, Y., Ma, Z., Gao, S., Chen, L., Zhong, H., Zhang, C., Li, T., Chen, W., Zhang, Y., & Lin, N. (2024). Osteoking promotes bone formation and bone defect repair through ZBP1-STAT1-PKR-MLKL-mediated necroptosis. Chinese Medicine, 19(1), 13.","journal-title":"Chinese Medicine"},{"issue":"5","key":"5691_CR48","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1172\/JCI122462","volume":"130","author":"C Dees","year":"2020","unstructured":"Dees, C., P\u00f6tter, S., & Zhang, Y. (2020). TGF-\u03b2-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis. The Journal of clinical investigation, 130(5), 2347\u20132363.","journal-title":"The Journal of clinical investigation"},{"issue":"4","key":"5691_CR49","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.7150\/ijbs.89568","volume":"20","author":"X Xin","year":"2024","unstructured":"Xin, X., Cheng, X., & Zeng, F. (2024). The Role of TGF-\u03b2\/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis. International journal of biological sciences, 20(4), 1436\u20131451.","journal-title":"International journal of biological sciences"},{"key":"5691_CR50","doi-asserted-by":"crossref","unstructured":"Xie, W., Gao, X., & Zhao, L. (2024). IRF9 and STAT1 as biomarkers involved in T-cell immunity in atherosclerosis. Journal of Biosciences, 49, 84.","DOI":"10.1007\/s12038-024-00448-5"},{"issue":"10","key":"5691_CR51","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/s41419-018-1100-1","volume":"9","author":"YP Lv","year":"2018","unstructured":"Lv, Y. P., Peng, L. S., & Wang, Q. H. (2018). Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression. Cell death & disease, 9(10), 1034.","journal-title":"Cell death & disease"},{"issue":"5","key":"5691_CR52","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/cdd.2016.8","volume":"23","author":"Z Su","year":"2016","unstructured":"Su, Z., Yang, Z., Xie, L., DeWitt, J. P., & Chen, Y. (2016). Cancer therapy in the necroptosis era. Cell Death And Differentiation, 23(5), 748\u2013756.","journal-title":"Cell Death And Differentiation"},{"issue":"6","key":"5691_CR53","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s12272-014-0385-6","volume":"37","author":"JH Bae","year":"2014","unstructured":"Bae, J. H., Shim, J. H., & Cho, Y. S. (2014). Chemical regulation of signaling pathways to programmed necrosis. Archives Of Pharmacal Research, 37(6), 689\u2013697.","journal-title":"Archives Of Pharmacal Research"},{"issue":"4","key":"5691_CR54","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/mco2.108","volume":"2","author":"X Liu","year":"2021","unstructured":"Liu, X., Xie, X., Ren, Y., Shao, Z., Zhang, N., Li, L., Ding, X., & Zhang, L. (2021). The role of necroptosis in disease and treatment. MedComm (2020), 2(4), 730\u2013755.","journal-title":"MedComm (2020)"},{"issue":"6","key":"5691_CR55","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1038\/s41418-021-00785-0","volume":"28","author":"S Martens","year":"2021","unstructured":"Martens, S., Bridelance, J., Roelandt, R., Vandenabeele, P., & Takahashi, N. (2021). MLKL in cancer: more than a necroptosis regulator. Cell Death And Differentiation, 28(6), 1757\u20131772.","journal-title":"Cell Death And Differentiation"},{"key":"5691_CR56","doi-asserted-by":"publisher","first-page":"105297","DOI":"10.1016\/j.phrs.2020.105297","volume":"163","author":"L Cao","year":"2021","unstructured":"Cao, L., & Mu, W. (2021). Necrostatin-1 and necroptosis inhibition: Pathophysiology and therapeutic implications. Pharmacological Research, 163, 105297.","journal-title":"Pharmacological Research"},{"issue":"2","key":"5691_CR57","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/s43440-023-00450-y","volume":"75","author":"H Ushijima","year":"2023","unstructured":"Ushijima, H., & Monzaki, R. (2023). An in vitro evaluation of the antioxidant activities of necroptosis and apoptosis inhibitors: the potential of necrostatin-1 and necrostatin-1i to have radical scavenging activities. Pharmacological Reports: Pr, 75(2), 490\u2013497.","journal-title":"Pharmacological Reports: Pr"},{"issue":"5","key":"5691_CR58","first-page":"2565","volume":"41","author":"R Chen","year":"2018","unstructured":"Chen, R., Xu, J., She, Y., Jiang, T., Zhou, S., Shi, H., & Li, C. (2018). Necrostatin-1 protects C2C12 myotubes from CoCl2-induced hypoxia. International Journal Of Molecular Medicine, 41(5), 2565\u20132572.","journal-title":"International Journal Of Molecular Medicine"}],"container-title":["Applied Biochemistry and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12010-026-05691-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12010-026-05691-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12010-026-05691-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:04:46Z","timestamp":1782104686000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12010-026-05691-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":58,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["5691"],"URL":"https:\/\/doi.org\/10.1007\/s12010-026-05691-0","relation":{},"ISSN":["0273-2289","1559-0291"],"issn-type":[{"value":"0273-2289","type":"print"},{"value":"1559-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"2 April 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the ethics committee of the First Affiliated Hospital of Dalian Medical University (PJ-KS-KY-2024-16). All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The experiments on mice were approved by the Animal Use and Care Committee of Dalian Medical University (No. AEE22208, the Ethics Committee of Dalian Medical University). The experiments on mice conformed all methods were performed in accordance with the relevant guidelines and regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines (\n                      \n                      ).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"ARRIVE guidelines statement"}}]}}