{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:26:14Z","timestamp":1793748374833,"version":"4.6.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"45","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2026,11,25]]},"DOI":"10.1038\/s41388-026-04012-3","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:36:22Z","timestamp":1791668182000},"page":"4916-4926","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adrenomedullin 2 drives intratumoral cancer cell invasion, intravasation and metastasis"],"prefix":"10.1038","volume":"45","author":[{"given":"Konstantin","family":"Stoletov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-2980","authenticated-orcid":false,"given":"Seyedeh Sara","family":"Karimian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-2225","authenticated-orcid":false,"given":"Alice","family":"Amitrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishwa","family":"Ranjan Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varinder Madhav","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0543-1339","authenticated-orcid":false,"given":"Amirali B.","family":"Bukhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suellen","family":"Lamb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-1459","authenticated-orcid":false,"given":"Konstantinos","family":"Konstantopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gane Ka-Shu","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-1204","authenticated-orcid":false,"given":"John D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"4012_CR1","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.4161\/cc.5.16.2864","volume":"5","author":"JL Townson","year":"2006","unstructured":"Townson JL, Chambers AF. Dormancy of solitary metastatic cells. Cell Cycle. 2006;5:1744\u201350.","journal-title":"Cell Cycle"},{"key":"4012_CR2","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.cell.2016.11.037","volume":"168","author":"AW Lambert","year":"2017","unstructured":"Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168:670\u201391.","journal-title":"Cell"},{"key":"4012_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41568-022-00527-5","volume":"23","author":"D Entenberg","year":"2023","unstructured":"Entenberg D, Oktay MH, Condeelis JS. Intravital imaging to study cancer progression and metastasis. Nat Rev Cancer. 2023;23:25\u201342.","journal-title":"Nat Rev Cancer"},{"key":"4012_CR4","first-page":"2504","volume":"60","author":"JB Wyckoff","year":"2000","unstructured":"Wyckoff JB, Jones JG, Condeelis JS, Segall JE. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res. 2000;60:2504\u201311.","journal-title":"Cancer Res"},{"key":"4012_CR5","doi-asserted-by":"publisher","first-page":"4336","DOI":"10.1111\/febs.16046","volume":"289","author":"MK Sznurkowska","year":"2022","unstructured":"Sznurkowska MK, Aceto N. The gate to metastasis: key players in cancer cell intravasation. FEBS J. 2022;289:4336\u201354.","journal-title":"FEBS J"},{"key":"4012_CR6","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2014.07.013","volume":"158","author":"N Aceto","year":"2014","unstructured":"Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158:1110\u201322.","journal-title":"Cell"},{"key":"4012_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108105","volume":"32","author":"C Donato","year":"2020","unstructured":"Donato C, Kunz L, Castro-Giner F, Paasinen-Sohns A, Strittmatter K, Szczerba BM, et al. Hypoxia triggers the intravasation of clustered circulating tumor cells. Cell Rep. 2020;32:108105.","journal-title":"Cell Rep"},{"key":"4012_CR8","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260285","volume":"136","author":"K Stoletov","year":"2023","unstructured":"Stoletov K, Sumanasekera C, Huh SJ, Jermihov A, Blakey JD, Chua KN, et al. Intravital imaging of Wnt\/\u03b2-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis. J Cell Sci. 2023;136:jcs260285.","journal-title":"J Cell Sci"},{"key":"4012_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04743-2","volume":"9","author":"K Stoletov","year":"2018","unstructured":"Stoletov K, Beatty PH, Lewis JD. Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis. Nat Commun. 2018;9:2343.","journal-title":"Nat Commun"},{"key":"4012_CR10","first-page":"62077","volume":"168","author":"K Stoletov","year":"2021","unstructured":"Stoletov K, Willetts L, Beatty PH, Lewis JD. Discovery of metastatic regulators using a rapid and quantitative intravital chick chorioallantoic membrane model. J Vis Exp. 2021;168:62077.","journal-title":"J Vis Exp"},{"key":"4012_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/978-1-59745-249-6_8","volume":"468","author":"TL Biechele","year":"2008","unstructured":"Biechele TL, Moon RT. Assaying beta-catenin\/TCF transcription with beta-catenin\/TCF transcription-based reporter constructs. Methods Mol Biol. 2008;468:99\u2013110.","journal-title":"Methods Mol Biol"},{"key":"4012_CR12","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/dvdy.22500","volume":"240","author":"B Ohkawara","year":"2011","unstructured":"Ohkawara B, Niehrs C. An ATF2-based luciferase reporter to monitor non-canonical Wnt signaling in Xenopus embryos. Dev Dyn. 2011;240:188\u201394.","journal-title":"Dev Dyn"},{"key":"4012_CR13","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.12688\/f1000research.15931.1","volume":"7","author":"SW Wingett","year":"2018","unstructured":"Wingett SW, Andrews S. FastQ Screen: a tool for multi-genome mapping and quality control. F1000Res. 2018;7:1338.","journal-title":"F1000Res"},{"key":"4012_CR14","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114\u201320.","journal-title":"Bioinformatics"},{"key":"4012_CR15","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12:357\u201360.","journal-title":"Nat Methods"},{"key":"4012_CR16","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923\u201330.","journal-title":"Bioinformatics"},{"key":"4012_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29","volume":"15","author":"CW Law","year":"2014","unstructured":"Law CW, Chen Y, Shi W, Smyth GK. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014;15:R29.","journal-title":"Genome Biol"},{"key":"4012_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 2010;11:R25.","journal-title":"Genome Biol"},{"key":"4012_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/sj.bjc.6602832","volume":"94","author":"LL Nikitenko","year":"2006","unstructured":"Nikitenko LL, Fox SB, Kehoe S, Rees MCP, Bicknell R. Adrenomedullin and tumour angiogenesis. Br J Cancer. 2006;94:1\u20137.","journal-title":"Br J Cancer"},{"key":"4012_CR20","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1158\/1535-7163.MCT-20-0619","volume":"20","author":"L Huang","year":"2021","unstructured":"Huang L, Wang D, Feng Z, Zhao H, Xiao F, Wei Y, et al. Inhibition of Intermedin (Adrenomedullin 2) suppresses the growth of glioblastoma and increases the antitumor activity of temozolomide. Mol Cancer Ther. 2021;20:284\u201395.","journal-title":"Mol Cancer Ther"},{"key":"4012_CR21","doi-asserted-by":"publisher","first-page":"5909","DOI":"10.3390\/cancers14235909","volume":"14","author":"Z Benyahia","year":"2022","unstructured":"Benyahia Z, Gaudy-Marqueste C, Berenguer-Daiz\u00e9 C, Chabane N, Dussault N, Cayol M, et al. Adrenomedullin secreted by melanoma cells promotes melanoma tumor growth through angiogenesis and lymphangiogenesis. Cancers. 2022;14:5909.","journal-title":"Cancers"},{"key":"4012_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10549-022-06687-0","volume":"195","author":"L Kong","year":"2022","unstructured":"Kong L, Xiong Y, Wang D, Huang L, Li M, Feng Z, et al. Intermedin (adrenomedullin 2) promotes breast cancer metastasis via Src\/c-Myc-mediated ribosome production and protein translation. Breast Cancer Res Treat. 2022;195:91\u2013103.","journal-title":"Breast Cancer Res Treat"},{"key":"4012_CR23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/ijc.22596","volume":"121","author":"S Keleg","year":"2007","unstructured":"Keleg S, Kayed H, Jiang X, Penzel R, Giese T, B\u00fcchler MW, et al. Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion. Int J Cancer. 2007;121:21\u201332.","journal-title":"Int J Cancer"},{"key":"4012_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/jme.1.01594","volume":"34","author":"J Bailey","year":"2005","unstructured":"Bailey J, Tyson-Capper AJ, Gilmore K, Robson SC, Europe-Finner GN. Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREMalpha and CREMtau2alpha) proteins. J Mol Endocrinol. 2005;34:1\u201317.","journal-title":"J Mol Endocrinol"},{"key":"4012_CR25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh3457","volume":"7","author":"CL Yankaskas","year":"2021","unstructured":"Yankaskas CL, Thompson KN, Paul CD, Vitolo MI, Mistriotis P, Mahendra A, et al. The fluid shear stress sensor TRPM7 regulates tumor cell intravasation. Sci Adv. 2021;7:eabh3457.","journal-title":"Sci Adv"},{"key":"4012_CR26","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Li T, Liu Z, Wang Z, Xie C, Li B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98\u2013102.","journal-title":"Nucleic Acids Res"},{"key":"4012_CR27","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1158\/0008-5472.CAN-06-3362","volume":"67","author":"V Ramachandran","year":"2007","unstructured":"Ramachandran V, Arumugam T, Hwang RF, Greenson JK, Simeone DM, Logsdon CD. Adrenomedullin is expressed in pancreatic cancer and stimulates cell proliferation and invasion in an autocrine manner via the adrenomedullin receptor, ADMR. Cancer Res. 2007;67:2666\u201375.","journal-title":"Cancer Res"},{"key":"4012_CR28","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1002\/ijc.28542","volume":"134","author":"L Wang","year":"2014","unstructured":"Wang L, Gala M, Yamamoto M, Pino MS, Kikuchi H, Shue DS, et al. Adrenomedullin is a therapeutic target in colorectal cancer. Int J Cancer. 2014;134:2041\u201350.","journal-title":"Int J Cancer"},{"key":"4012_CR29","doi-asserted-by":"publisher","first-page":"4327","DOI":"10.3892\/ol.2017.5959","volume":"13","author":"T Cho","year":"2017","unstructured":"Cho T, Shiozawa E, Urushibara F, Arai N, Funaki T, Takehara Y, et al. The role of microvessel density, lymph node metastasis, and tumor size as prognostic factors of distant metastasis in colorectal cancer. Oncol Lett. 2017;13:4327\u201333.","journal-title":"Oncol Lett"},{"key":"4012_CR30","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/jso.1164","volume":"78","author":"T Yamamura","year":"2001","unstructured":"Yamamura T, Tsukikawa S, Yamada K, Yamaguchi S. Morphologic analysis of microvessels in colorectal tumors with respect to the formation of liver metastases. J Surg Oncol. 2001;78:259\u201364.","journal-title":"J Surg Oncol"},{"key":"4012_CR31","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.ccell.2024.03.013","volume":"42","author":"W Wang","year":"2024","unstructured":"Wang W, Li T, Cheng Y, Li F, Qi S, Mao M, et al. Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization. Cancer Cell. 2024;42:815\u201332.e12.","journal-title":"Cancer Cell"},{"key":"4012_CR32","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1021\/acsptsci.0c00032","volume":"3","author":"P Avgoustou","year":"2020","unstructured":"Avgoustou P, Jailani ABA, Zirimwabagabo JO, Tozer MJ, Gibson KR, Glossop PA, et al. Discovery of a first-in-class potent small molecule antagonist against the adrenomedullin-2 receptor. ACS Pharmacol Transl Sci. 2020;3:706\u201319.","journal-title":"ACS Pharmacol Transl Sci"},{"key":"4012_CR33","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1080\/17460441.2022.2090541","volume":"17","author":"ABA Jailani","year":"2022","unstructured":"Jailani ABA, Bigos KJA, Avgoustou P, Egan JL, Hathway RA, Skerry TM, et al. Targeting the adrenomedullin-2 receptor for the discovery and development of novel anti-cancer agents. Expert Opin Drug Discov. 2022;17:839\u201348.","journal-title":"Expert Opin Drug Discov"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-04012-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-04012-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-04012-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:03:29Z","timestamp":1793747009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-04012-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":33,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2026,11,25]]}},"alternative-id":["4012"],"URL":"https:\/\/doi.org\/10.1038\/s41388-026-04012-3","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"assertion":[{"value":"4 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}