{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T02:40:13Z","timestamp":1794451213476,"version":"4.9.1"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["09\/716(0188)\/2019-EMR-I"],"award-info":[{"award-number":["09\/716(0188)\/2019-EMR-I"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR14379\/Med\/30\/536\/2010"],"award-info":[{"award-number":["BT\/PR14379\/Med\/30\/536\/2010"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Anusandhan National Research Foundation","doi-asserted-by":"crossref","award":["SR\/S0\/HS\/0133\/2010"],"award-info":[{"award-number":["SR\/S0\/HS\/0133\/2010"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-026-02788-1","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:16:26Z","timestamp":1773224186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EPHA2-Ephrin-B1 cis-interaction drives an oncogenic reverse signaling, leading to the recurrence of oral cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Reshma","family":"Raj R","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Krishnan U","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Shanmugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiss Maria","family":"Louis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravichandran Damodaran","family":"Jeyaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshava K.","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsha","family":"Gowda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghna","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumathy G.","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothy S.","family":"Prabhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafsa","family":"Shabeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balagopal","family":"P. G","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thameem","family":"A","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Jose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu Sunil","family":"Jaikumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessy Thomas","family":"Maliekal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"issue":"1","key":"2788_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41568-023-00634-x","volume":"24","author":"EB Pasquale","year":"2024","unstructured":"Pasquale EB. Eph receptors and ephrins in cancer progression. Nat Rev Cancer. 2024;24(1):5\u201327.","journal-title":"Nat Rev Cancer"},{"issue":"8-9","key":"2788_CR2","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1387\/ijdb.041899fm","volume":"48","author":"F Mann","year":"2004","unstructured":"Mann F, Harris WA, Holt CE. New views on retinal axon development: a navigation guide. Int J Dev Biol. 2004;48(8\u20139):957\u201364.","journal-title":"Int J Dev Biol"},{"issue":"3","key":"2788_CR3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.4103\/1673-5374.266044","volume":"15","author":"M Medori","year":"2020","unstructured":"Medori M, Spelzini G, Scicolone G. Molecular complexity of visual mapping: a challenge for regenerating therapy. Neural Regen Res. 2020;15(3):382\u20139.","journal-title":"Neural Regen Res"},{"issue":"6739","key":"2788_CR4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/21907","volume":"400","author":"G Mellitzer","year":"1999","unstructured":"Mellitzer G, Xu Q, Wilkinson DG. Eph receptors and ephrins restrict cell intermingling and communication. Nature. 1999;400(6739):77\u201381.","journal-title":"Nature"},{"issue":"9","key":"2788_CR5","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1177\/0022034509342363","volume":"88","author":"A Arthur","year":"2009","unstructured":"Arthur A, Koblar S, Shi S, Gronthos S. Eph\/ephrinB mediate dental pulp stem cell mobilization and function. J Dent Res. 2009;88(9):829\u201334.","journal-title":"J Dent Res"},{"issue":"9","key":"2788_CR6","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1161\/CIRCRESAHA.110.239459","volume":"108","author":"P Goichberg","year":"2011","unstructured":"Goichberg P, Bai Y, D\u2019Amario D, Ferreira-Martins J, Fiorini C, Zheng H, et al. The ephrin A1-EphA2 system promotes cardiac stem cell migration after infarction. Circ Res. 2011;108(9):1071\u201383.","journal-title":"Circ Res"},{"issue":"2","key":"2788_CR7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0092-8674(02)01015-2","volume":"111","author":"E Batlle","year":"2002","unstructured":"Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB\/ephrinB. Cell. 2002;111(2):251\u201363.","journal-title":"Cell"},{"issue":"11","key":"2788_CR8","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/ncb3045","volume":"16","author":"C Ottone","year":"2014","unstructured":"Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, et al. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol. 2014;16(11):1045\u201356.","journal-title":"Nat Cell Biol"},{"issue":"3","key":"2788_CR9","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/jcb.25000","volume":"116","author":"K Chen","year":"2015","unstructured":"Chen K, Bai H, Liu Y, Hoyle DL, Shen WF, Wu LQ, et al. EphB4 forward-signaling regulates cardiac progenitor development in mouse ES cells. J Cell Biochem. 2015;116(3):467\u201375.","journal-title":"J Cell Biochem"},{"key":"2788_CR10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.exphem.2018.10.004","volume":"69","author":"A Arthur","year":"2019","unstructured":"Arthur A, Nguyen TM, Paton S, Zannettino ACW, Gronthos S. Loss of EfnB1 in the osteogenic lineage compromises their capacity to support hematopoietic stem\/progenitor cell maintenance. Exp Hematol. 2019;69:43\u201353.","journal-title":"Exp Hematol"},{"issue":"Pt 1","key":"2788_CR11","first-page":"120293","volume":"264","author":"K Yi","year":"2024","unstructured":"Yi K, Chen W, Zhou X, Xie C, Zhong C, Zhu J. Bisphenol S exposure promoted stemness of triple-negative breast cancer cells via regulating Gli1-mediated Sonic hedgehog pathway. Environ Res. 2024;264(Pt 1):120293.","journal-title":"Environ Res"},{"issue":"1","key":"2788_CR12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.cell.2005.01.020","volume":"121","author":"T Marquardt","year":"2005","unstructured":"Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T, et al. Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains. Cell. 2005;121(1):127\u201339.","journal-title":"Cell"},{"issue":"1","key":"2788_CR13","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.neuron.2011.05.031","volume":"71","author":"TJ Kao","year":"2011","unstructured":"Kao TJ, Kania A. Ephrin-mediated cis-attenuation of Eph receptor signaling is essential for spinal motor axon guidance. Neuron. 2011;71(1):76\u201391.","journal-title":"Neuron"},{"issue":"11","key":"2788_CR14","doi-asserted-by":"publisher","first-page":"e81445","DOI":"10.1371\/journal.pone.0081445","volume":"8","author":"G Falivelli","year":"2013","unstructured":"Falivelli G, Lisabeth EM, de la Rubio Torre E, Perez-Tenorio G, Tosato G, Salvucci O, et al. Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands. PLoS ONE. 2013;8(11):e81445.","journal-title":"PLoS ONE"},{"key":"2788_CR15","doi-asserted-by":"publisher","first-page":"809364","DOI":"10.3389\/fmolb.2021.809364","volume":"8","author":"A Cecchini","year":"2021","unstructured":"Cecchini A, Cornelison DDW. Eph\/Ephrin-Based Protein Complexes: The Importance of cis Interactions in Guiding Cellular Processes. Front Mol Biosci. 2021;8:809364.","journal-title":"Front Mol Biosci"},{"issue":"1","key":"2788_CR16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12964-024-01580-3","volume":"22","author":"X Guo","year":"2024","unstructured":"Guo X, Yang Y, Tang J, Xiang J. Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity. Cell Commun Signal. 2024;22(1):299.","journal-title":"Cell Commun Signal"},{"issue":"3","key":"2788_CR17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrc2806","volume":"10","author":"EB Pasquale","year":"2010","unstructured":"Pasquale EB. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer. 2010;10(3):165\u201380.","journal-title":"Nat Rev Cancer"},{"issue":"9","key":"2788_CR18","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.2174\/156800911798073050","volume":"11","author":"R Biao-xue","year":"2011","unstructured":"Biao-xue R, Xi-guang C, Shuan-ying Y, Wei L, Zong-juan M. EphA2-dependent molecular targeting therapy for malignant tumors. Curr Cancer Drug Targets. 2011;11(9):1082\u201397.","journal-title":"Curr Cancer Drug Targets"},{"key":"2788_CR19","doi-asserted-by":"publisher","first-page":"788587","DOI":"10.3389\/fcell.2022.788587","volume":"10","author":"W Liu","year":"2022","unstructured":"Liu W, Yu C, Li J, Fang J. The Roles of EphB2 in Cancer. Front Cell Dev Biol. 2022;10:788587.","journal-title":"Front Cell Dev Biol"},{"issue":"16","key":"2788_CR20","doi-asserted-by":"publisher","first-page":"8412","DOI":"10.3390\/ijms22168412","volume":"22","author":"A Pergaris","year":"2021","unstructured":"Pergaris A, Danas E, Goutas D, Sykaras AG, Soranidis A, Theocharis S. The clinical impact of the EPH\/Ephrin system in cancer: unwinding the thread. Int J Mol Sci. 2021;22(16):8412.","journal-title":"Int J Mol Sci."},{"issue":"1","key":"2788_CR21","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1007\/s12672-024-01380-8","volume":"15","author":"C Qiu","year":"2024","unstructured":"Qiu C, Sun N, Zeng S, Chen L, Gong F, Tian J, et al. Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review. Discov Oncol. 2024;15(1):501.","journal-title":"Discov Oncol"},{"issue":"4","key":"2788_CR22","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s00109-024-02431-x","volume":"102","author":"RN Veiga","year":"2024","unstructured":"Veiga RN, de Azevedo ALK, de Oliveira JC, Gradia DF. Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer. J Mol Med (Berl). 2024;102(4):479\u201393.","journal-title":"J Mol Med (Berl)"},{"issue":"6","key":"2788_CR23","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.ccr.2012.11.005","volume":"22","author":"E Binda","year":"2012","unstructured":"Binda E, Visioli A, Giani F, Lamorte G, Copetti M, Pitter KL, et al. The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas. Cancer Cell. 2012;22(6):765\u201380.","journal-title":"Cancer Cell"},{"issue":"9","key":"2788_CR24","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1158\/0008-5472.CAN-13-2136","volume":"74","author":"W Song","year":"2014","unstructured":"Song W, Ma Y, Wang J, Brantley-Sieders D, Chen J. JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer. Cancer Res. 2014;74(9):2444\u201354.","journal-title":"Cancer Res"},{"key":"2788_CR25","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.canlet.2018.12.011","volume":"444","author":"JY Li","year":"2019","unstructured":"Li JY, Xiao T, Yi HM, Yi H, Feng J, Zhu JF, et al. S897 phosphorylation of EphA2 is indispensable for EphA2-dependent nasopharyngeal carcinoma cell invasion, metastasis and stem properties. Cancer Lett. 2019;444:162\u201374.","journal-title":"Cancer Lett"},{"issue":"1","key":"2788_CR26","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1007\/s00018-024-05325-w","volume":"81","author":"J Bai","year":"2024","unstructured":"Bai J, Chen Y, Sun Y, Wang X, Wang Y, Guo S, et al. EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma. Cell Mol Life Sci. 2024;81(1):278.","journal-title":"Cell Mol Life Sci"},{"issue":"6","key":"2788_CR27","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.7150\/ijbs.82567","volume":"19","author":"P Zhao","year":"2023","unstructured":"Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, et al. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci. 2023;19(6):1861\u201374.","journal-title":"Int J Biol Sci"},{"issue":"4","key":"2788_CR28","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.bbrc.2018.04.020","volume":"499","author":"Y Hamaoka","year":"2018","unstructured":"Hamaoka Y, Negishi M, Katoh H. Tyrosine kinase activity of EphA2 promotes its S897 phosphorylation and glioblastoma cell proliferation. Biochem Biophys Res Commun. 2018;499(4):920\u20136.","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"2788_CR29","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.humpath.2006.02.021","volume":"37","author":"J Castellvi","year":"2006","unstructured":"Castellvi J, Garcia A, de la Torre J, Hernandez J, Gil A, Xercavins J, et al. Ephrin B expression in epithelial ovarian neoplasms correlates with tumor differentiation and angiogenesis. Hum Pathol. 2006;37(7):883\u20139.","journal-title":"Hum Pathol"},{"issue":"1","key":"2788_CR30","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1186\/s12935-021-02226-x","volume":"21","author":"M Deng","year":"2021","unstructured":"Deng M, Tong R, Zhang Z, Wang T, Liang C, Zhou X, et al. EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma. Cancer Cell Int. 2021;21(1):535.","journal-title":"Cancer Cell Int"},{"issue":"3","key":"2788_CR31","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.21037\/jgo-24-227","volume":"15","author":"Q Ye","year":"2024","unstructured":"Ye Q, Chen D, Liu X, Yang B, Li G, Ma J, et al. The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis. J Gastrointest Oncol. 2024;15(3):1165\u201378.","journal-title":"J Gastrointest Oncol"},{"issue":"2","key":"2788_CR32","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1002\/cam4.4987","volume":"12","author":"R Yiminniyaze","year":"2023","unstructured":"Yiminniyaze R, Zhang X, Zhu N, Wang J, Li C, Wumaier G, et al. EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma. Cancer Med. 2023;12(2):1630\u201342.","journal-title":"Cancer Med"},{"key":"2788_CR33","doi-asserted-by":"publisher","first-page":"796592","DOI":"10.3389\/fgene.2021.796592","volume":"12","author":"P Zheng","year":"2021","unstructured":"Zheng P, Liu X, Li H, Gao L, Yu Y, Wang N, et al. EFNA3 Is a Prognostic Biomarker Correlated With Immune Cell Infiltration and Immune Checkpoints in Gastric Cancer. Front Genet. 2021;12:796592.","journal-title":"Front Genet"},{"issue":"1","key":"2788_CR34","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s12672-025-01867-y","volume":"16","author":"Y Zheng","year":"2025","unstructured":"Zheng Y, Shi J. EFNB1 drives glioma progression and shapes the immune microenvironment: a potential prognostic biomarker. Discov Oncol. 2025;16(1):249.","journal-title":"Discov Oncol"},{"issue":"1","key":"2788_CR35","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1634\/stemcells.2006-0373","volume":"25","author":"A Stokowski","year":"2007","unstructured":"Stokowski A, Shi S, Sun T, Bartold PM, Koblar SA, Gronthos S. EphB\/ephrin-B interaction mediates adult stem cell attachment, spreading, and migration: implications for dental tissue repair. Stem Cells. 2007;25(1):156\u201364.","journal-title":"Stem Cells"},{"issue":"2","key":"2788_CR36","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/cpr.12172","volume":"48","author":"L Zhu","year":"2015","unstructured":"Zhu L, Dissanayaka WL, Green DW, Zhang C. Stimulation of EphB2\/ephrin-B1 signalling by tumour necrosis factor alpha in human dental pulp stem cells. Cell Prolif. 2015;48(2):231\u20138.","journal-title":"Cell Prolif"},{"issue":"32","key":"2788_CR37","doi-asserted-by":"publisher","first-page":"11472","DOI":"10.1523\/JNEUROSCI.6349-10.2011","volume":"31","author":"T Catchpole","year":"2011","unstructured":"Catchpole T, Henkemeyer M. EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche. J Neurosci. 2011;31(32):11472\u201383.","journal-title":"J Neurosci"},{"key":"2788_CR38","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3389\/fonc.2020.00283","volume":"10","author":"MV Mencucci","year":"2020","unstructured":"Mencucci MV, Lapyckyj L, Rosso M, Besso MJ, Belgorosky D, Isola M, et al. Ephrin-B1 is a novel biomarker of bladder cancer aggressiveness. Studies in murine models and in human samples. Front Oncol. 2020;10:283.","journal-title":"Front Oncol"},{"key":"2788_CR39","doi-asserted-by":"publisher","first-page":"788024","DOI":"10.3389\/fonc.2021.788024","volume":"11","author":"D Dharmapal","year":"2021","unstructured":"Dharmapal D, Jyothy A, Mohan A, Balagopal PG, George NA, Sebastian P, et al. beta-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells. Front Oncol. 2021;11:788024.","journal-title":"Front Oncol"},{"issue":"11","key":"2788_CR40","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/ng.2007.11","volume":"39","author":"C Cortina","year":"2007","unstructured":"Cortina C, Palomo-Ponce S, Iglesias M, Fernandez-Masip JL, Vivancos A, Whissell G, et al. EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet. 2007;39(11):1376\u201383.","journal-title":"Nat Genet"},{"issue":"12","key":"2788_CR41","doi-asserted-by":"publisher","first-page":"e28674","DOI":"10.1371\/journal.pone.0028674","volume":"6","author":"OM Subach","year":"2011","unstructured":"Subach OM, Cranfill PJ, Davidson MW, Verkhusha VV. An enhanced monomeric blue fluorescent protein with the high chemical stability of the chromophore. PLoS ONE. 2011;6(12):e28674.","journal-title":"PLoS ONE"},{"issue":"5","key":"2788_CR42","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nmeth.1207","volume":"5","author":"HW Ai","year":"2008","unstructured":"Ai HW, Hazelwood KL, Davidson MW, Campbell RE. Fluorescent protein FRET pairs for ratiometric imaging of dual biosensors. Nat Methods. 2008;5(5):401\u20133.","journal-title":"Nat Methods"},{"issue":"11","key":"2788_CR43","doi-asserted-by":"publisher","first-page":"4670","DOI":"10.1021\/pr800215n","volume":"7","author":"TZ Kristiansen","year":"2008","unstructured":"Kristiansen TZ, Harsha HC, Gronborg M, Maitra A, Pandey A. Differential membrane proteomics using 18O-labeling to identify biomarkers for cholangiocarcinoma. J Proteome Res. 2008;7(11):4670\u20137.","journal-title":"J Proteome Res"},{"key":"2788_CR44","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/978-1-62703-392-3_16","volume":"1007","author":"HC Harsha","year":"2013","unstructured":"Harsha HC, Pinto SM, Pandey A. Proteomic strategies to characterize signaling pathways. Methods Mol Biol. 2013;1007:359\u201377.","journal-title":"Methods Mol Biol"},{"issue":"2","key":"2788_CR45","doi-asserted-by":"publisher","first-page":"111551","DOI":"10.1016\/j.yexcr.2019.111551","volume":"383","author":"G Shanmugam","year":"2019","unstructured":"Shanmugam G, Mohan A, Kumari K, Louis JM, Soumya Krishnan U, Balagopal PG, et al. A novel reporter construct for screening small molecule inhibitors that specifically target self-renewing cancer cells. Exp Cell Res. 2019;383(2):111551.","journal-title":"Exp Cell Res"},{"issue":"1-2","key":"2788_CR46","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","volume":"347","author":"Y Hu","year":"2009","unstructured":"Hu Y, Smyth GK. ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009;347(1\u20132):70\u20138.","journal-title":"J Immunol Methods"},{"issue":"2","key":"2788_CR47","doi-asserted-by":"publisher","first-page":"114166","DOI":"10.1016\/j.yexcr.2024.114166","volume":"441","author":"M Sarkar","year":"2024","unstructured":"Sarkar M, Raj RR, Maliekal TT. Finding the partner: FRET and beyond. Exp Cell Res. 2024;441(2):114166.","journal-title":"Exp Cell Res"},{"issue":"5","key":"2788_CR48","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.1007\/s12070-024-04889-0","volume":"76","author":"S Jain","year":"2024","unstructured":"Jain S, Dhall K, Brar GS, Gupta S, Jain K, Garg N, et al. Outcome of upfront surgically resected patients of oral tongue squamous cell carcinoma and factors affecting it: experience from tertiary care facility in North India. Indian J Otolaryngol Head Neck Surg. 2024;76(5):4479\u201386.","journal-title":"Indian J Otolaryngol Head Neck Surg"},{"issue":"1","key":"2788_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4174\/astr.2023.104.1.1","volume":"104","author":"YJ Lee","year":"2023","unstructured":"Lee YJ, Jung SP, Bae JW, Yang SM, You JY, Bae SY. Prognosis according to the timing of recurrence in breast cancer. Ann Surg Treat Res. 2023;104(1):1\u20139.","journal-title":"Ann Surg Treat Res"},{"key":"2788_CR50","doi-asserted-by":"publisher","first-page":"1793005","DOI":"10.1155\/2022\/1793005","volume":"2022","author":"H Zhao","year":"2022","unstructured":"Zhao H, Chen Z, Fang Y, Su M, Xu Y, Wang Z, et al. Prediction of Prognosis and Recurrence of Bladder Cancer by ECM-Related Genes. J Immunol Res. 2022;2022:1793005.","journal-title":"J Immunol Res"},{"issue":"7","key":"2788_CR51","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.21037\/tlcr-22-148","volume":"11","author":"WG Jeong","year":"2022","unstructured":"Jeong WG, Choi H, Chae KJ, Kim J. Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach. Transl Lung Cancer Res. 2022;11(7):1279\u201391.","journal-title":"Transl Lung Cancer Res"},{"issue":"11","key":"2788_CR52","doi-asserted-by":"publisher","first-page":"614","DOI":"10.5732\/cjc.012.10219","volume":"32","author":"B Wang","year":"2013","unstructured":"Wang B, Zhang S, Yue K, Wang XD. The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer. 2013;32(11):614\u20138.","journal-title":"Chin J Cancer"},{"issue":"1","key":"2788_CR53","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1186\/s12885-024-12118-8","volume":"24","author":"O Davaatsend","year":"2024","unstructured":"Davaatsend O, Altannamar M, Ganbat M, Jagdagsuren U. Factors associated with recurrence in patients with oral cancer in Mongolia. BMC Cancer. 2024;24(1):356.","journal-title":"BMC Cancer"},{"issue":"15","key":"2788_CR54","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.3390\/cancers16152730","volume":"16","author":"S Mirshahidi","year":"2024","unstructured":"Mirshahidi S, Yuan IJ, Chen Z, Simental A, Lee SC, Andrade Filho PA, et al. Tumor cell stemness and stromal cell features contribute to oral cancer outcome disparity in Black Americans. Cancers (Basel). 2024;16(15):2730.","journal-title":"Cancers (Basel)"},{"issue":"2","key":"2788_CR55","first-page":"29","volume":"19","author":"M Banki","year":"2023","unstructured":"Banki M, Moosavi MS. Umbrella review on cancer stem cell in oral and head and neck squamous cell carcinoma. J Stem Cells Regen Med. 2023;19(2):29\u201333.","journal-title":"J Stem Cells Regen Med"},{"issue":"6","key":"2788_CR56","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/S0168-8278(03)00498-7","volume":"39","author":"Y Sawai","year":"2003","unstructured":"Sawai Y, Tamura S, Fukui K, Ito N, Imanaka K, Saeki A, et al. Expression of ephrin-B1 in hepatocellular carcinoma: possible involvement in neovascularization. J Hepatol. 2003;39(6):991\u20136.","journal-title":"J Hepatol"},{"issue":"Pt 1","key":"2788_CR57","doi-asserted-by":"publisher","first-page":"128848","DOI":"10.1016\/j.ijbiomac.2023.128848","volume":"258","author":"Y Hu","year":"2024","unstructured":"Hu Y, Xie Q, Zhao J, Yang R, Qin J, Li H, et al. Interaction between the EPHB2 receptor and EFNB1 ligand drives gastric cancer invasion and metastasis via the Wnt\/beta-catenin\/FAK pathway. Int J Biol Macromol. 2024;258(Pt 1):128848.","journal-title":"Int J Biol Macromol"},{"issue":"5","key":"2788_CR58","first-page":"1220","volume":"13","author":"NN Phan","year":"2020","unstructured":"Phan NN, Liu S, Wang CY, Hsu HP, Lai MD, Li CY, et al. Overexpressed gene signature of EPH receptor A\/B family in cancer patients-comprehensive analyses from the public high-throughput database. Int J Clin Exp Pathol. 2020;13(5):1220\u201342.","journal-title":"Int J Clin Exp Pathol"},{"issue":"2","key":"2788_CR59","doi-asserted-by":"publisher","first-page":"101042831769100","DOI":"10.1177\/1010428317691000","volume":"39","author":"C Zhao","year":"2017","unstructured":"Zhao C, Wang A, Lu F, Chen H, Fu P, Zhao X, et al. Overexpression of junctional adhesion molecule-A and EphB2 predicts poor survival in lung adenocarcinoma patients. Tumour Biol. 2017;39(2):1010428317691000.","journal-title":"Tumour Biol"},{"issue":"12","key":"2788_CR60","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.1158\/0008-5472.CAN-21-0184","volume":"81","author":"HW Leung","year":"2021","unstructured":"Leung HW, Leung CON, Lau EY, Chung KPS, Mok EH, Lei MML, et al. EPHB2 activates beta-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma. Cancer Res. 2021;81(12):3229\u201340.","journal-title":"Cancer Res"},{"issue":"3","key":"2788_CR61","first-page":"1295","volume":"12","author":"H Kim","year":"2022","unstructured":"Kim H, Myung JK, Paik SS, Kim H, Park H, Kim YJ, et al. EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration. Am J Cancer Res. 2022;12(3):1295\u2013308.","journal-title":"Am J Cancer Res"},{"issue":"15","key":"2788_CR62","doi-asserted-by":"publisher","first-page":"8098","DOI":"10.3390\/ijms22158098","volume":"22","author":"AS Ebrahim","year":"2021","unstructured":"Ebrahim AS, Hailat Z, Bandyopadhyay S, Neill D, Kandouz M. The value of EphB2 receptor and cognate ephrin ligands in prognostic and predictive assessments of human breast cancer. Int J Mol Sci. 2021;22(15):8098.","journal-title":"Int J Mol Sci"},{"issue":"5","key":"2788_CR63","doi-asserted-by":"publisher","first-page":"298","DOI":"10.4132\/jptm.2018.06.29","volume":"52","author":"BG Jang","year":"2018","unstructured":"Jang BG, Kim HS, Chang WY, Bae JM, Kang GH. Prognostic significance of EPHB2 expression in colorectal cancer progression. J Pathol Transl Med. 2018;52(5):298\u2013306.","journal-title":"J Pathol Transl Med"},{"issue":"9","key":"2788_CR64","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.3390\/cancers14092336","volume":"14","author":"M Kakarla","year":"2022","unstructured":"Kakarla M, ChallaSivaKanaka S, Dufficy MF, Gil V, Filipovich Y, Vickman R, et al. Ephrin B activate Src family kinases in fibroblasts inducing stromal remodeling in prostate cancer. Cancers (Basel). 2022;14(9):2336.","journal-title":"Cancers (Basel)"},{"key":"2788_CR65","doi-asserted-by":"publisher","first-page":"109668","DOI":"10.1016\/j.cellsig.2020.109668","volume":"73","author":"MP Gehring","year":"2020","unstructured":"Gehring MP, Pasquale EB. Protein kinase C phosphorylates the EphA2 receptor on serine 892 in the regulatory linker connecting the kinase and SAM domains. Cell Signal. 2020;73:109668.","journal-title":"Cell Signal"},{"issue":"1","key":"2788_CR66","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ccr.2009.04.009","volume":"16","author":"H Miao","year":"2009","unstructured":"Miao H, Li DQ, Mukherjee A, Guo H, Petty A, Cutter J, et al. EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell. 2009;16(1):9\u201320.","journal-title":"Cancer Cell"},{"key":"2788_CR67","doi-asserted-by":"publisher","first-page":"7679","DOI":"10.1038\/ncomms8679","volume":"6","author":"Y Zhou","year":"2015","unstructured":"Zhou Y, Yamada N, Tanaka T, Hori T, Yokoyama S, Hayakawa Y, et al. Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2. Nat Commun. 2015;6:7679.","journal-title":"Nat Commun"},{"key":"2788_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2021.09.001","volume":"103-104","author":"AC Finney","year":"2021","unstructured":"Finney AC, Scott ML, Reeves KA, Wang D, Alfaidi M, Schwartz JC, et al. EphA2 signaling within integrin adhesions regulates fibrillar adhesion elongation and fibronectin deposition. Matrix Biol. 2021;103\u2013104:1\u201321.","journal-title":"Matrix Biol"},{"issue":"8","key":"2788_CR69","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41419-020-02831-0","volume":"11","author":"YP Xiang","year":"2020","unstructured":"Xiang YP, Xiao T, Li QG, Lu SS, Zhu W, Liu YY, et al. Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2\/Erk-1\/2 signaling pathway. Cell Death Dis. 2020;11(8):709.","journal-title":"Cell Death Dis"},{"issue":"1","key":"2788_CR70","doi-asserted-by":"publisher","first-page":"7047","DOI":"10.1038\/s41467-021-27343-z","volume":"12","author":"BC Lechtenberg","year":"2021","unstructured":"Lechtenberg BC, Gehring MP, Light TP, Horne CR, Matsumoto MW, Hristova K, et al. Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker. Nat Commun. 2021;12(1):7047.","journal-title":"Nat Commun"},{"issue":"23","key":"2788_CR71","doi-asserted-by":"publisher","first-page":"16017","DOI":"10.1074\/jbc.M709934200","volume":"283","author":"WB Fang","year":"2008","unstructured":"Fang WB, Brantley-Sieders DM, Hwang Y, Ham AJ, Chen J. Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase. J Biol Chem. 2008;283(23):16017\u201326.","journal-title":"J Biol Chem"},{"issue":"7","key":"2788_CR72","doi-asserted-by":"publisher","first-page":"4313","DOI":"10.1073\/pnas.052715699","volume":"99","author":"K Fujikawa","year":"2002","unstructured":"Fujikawa K, Inoue Y, Sakai M, Koyama Y, Nishi S, Funada R, et al. Vav3 is regulated during the cell cycle and effects cell division. Proc Natl Acad Sci U S A. 2002;99(7):4313\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2788_CR73","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1038\/s41416-024-02783-8","volume":"131","author":"K Hayashi","year":"2024","unstructured":"Hayashi K, Takagane K, Itoh G, Kuriyama S, Koyota S, Meguro K, et al. Cell-cell contact-dependent secretion of large-extracellular vesicles from EFNB(high) cancer cells accelerates peritoneal dissemination. Br J Cancer. 2024;131(6):982\u201395.","journal-title":"Br J Cancer"},{"issue":"5","key":"2788_CR74","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41419-021-03692-x","volume":"12","author":"Z Gao","year":"2021","unstructured":"Gao Z, Han X, Zhu Y, Zhang H, Tian R, Wang Z, et al. Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling. Cell Death Dis. 2021;12(5):414.","journal-title":"Cell Death Dis"},{"issue":"8","key":"2788_CR75","doi-asserted-by":"publisher","first-page":"e177599","DOI":"10.1172\/JCI177599","volume":"135","author":"SQ Liu","year":"2025","unstructured":"Liu SQ, Cheng XX, He S, Xia T, Li YQ, Peng W, et al. Super-enhancer-driven EFNA1 fuels tumor progression in cervical cancer via the FOSL2-Src\/AKT\/STAT3 axis. J Clin Invest. 2025;135(8):e177599. https:\/\/doi.org\/10.1172\/JCI177599.","journal-title":"J Clin Invest."},{"issue":"42","key":"2788_CR76","doi-asserted-by":"publisher","first-page":"38940","DOI":"10.1074\/jbc.M105815200","volume":"276","author":"MS Kalo","year":"2001","unstructured":"Kalo MS, Yu HH, Pasquale EB. In vivo tyrosine phosphorylation sites of activated ephrin-B1 and ephB2 from neural tissue. J Biol Chem. 2001;276(42):38940\u20138.","journal-title":"J Biol Chem"},{"issue":"3","key":"2788_CR77","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.neures.2003.11.009","volume":"48","author":"Y Yin","year":"2004","unstructured":"Yin Y, Yamashita Y, Noda H, Okafuji T, Go MJ, Tanaka H. EphA receptor tyrosine kinases interact with co-expressed ephrin-A ligands in cis. Neurosci Res. 2004;48(3):285\u201396.","journal-title":"Neurosci Res"},{"key":"2788_CR78","unstructured":"Kim S, Toth P, Wang W, Seiradake E, Shi X, Wang B. EphA2 and Ephrin-A1 utilize the same interface for both in cis and in trans interactions that differentially regulate cell signaling and function. bioRxiv. 2025."},{"issue":"6674","key":"2788_CR79","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1126\/science.adg5314","volume":"382","author":"X Shi","year":"2023","unstructured":"Shi X, Lingerak R, Herting CJ, Ge Y, Kim S, Toth P, et al. Time-resolved live-cell spectroscopy reveals EphA2 multimeric assembly. Science. 2023;382(6674):1042\u201350.","journal-title":"Science"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-02788-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02788-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02788-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:12:55Z","timestamp":1782803575000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-02788-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2788"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-02788-1","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"assertion":[{"value":"22 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"For the studies involving fresh oral cancer samples, the tumor tissues were collected after getting informed consent from the patients from the Regional Cancer Centre, Thiruvananthapuram. The protocol was approved by the Institute Human Ethical Committee of Rajiv Gandhi Centre for Biotechnology (IHEC\/1\/2011\/04), and Regional Cancer Centre, Thiruvananthapuram (HEC\/24\/2011). Paraffin embedded tissue blocks for making the tissue microarray (TMA) were collected from the archives of Cochin Cancer Research Centre, Cochin, and the preparation of TMA, IHC staining, scoring and imaging were done at St. Johns Research Institute. The protocol was approved by Institute Human Ethical Committee of all the respective study centers (IEC\/150\/2023, IHEC\/1112022_Exl11). All the animal experiments were conducted adhering to the ARRIVE guidelines, and as per the approved guidelines of the Institute Animal Ethics Committee (IAEC\/874\/TM\/2002, IAEC\/875\/TM\/2002 and IAEC\/894\/TM\/2002) which is under the Committee for the Control and Supervision of Experiments on Animals (CCSEA), Govt. of India. The ethical end points for studies involving orthotopic injection and subcutaneous injection, were\u2009<\u20091000 mm\n                      3\n                      . The recombinant DNA works were reviewed and approved by the Institutional Bio-safety Committee (71\/IBSC\/TTM\/2022, 72\/IBSC\/TTM\/2022, and 156\/IBSC\/TTM\/2024).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"300"}}