{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:15:35Z","timestamp":1790964935952,"version":"4.1.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2023-00242183"],"award-info":[{"award-number":["RS-2023-00242183"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2020R1A6A1A03043539"],"award-info":[{"award-number":["2020R1A6A1A03043539"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2023-00221174"],"award-info":[{"award-number":["RS-2023-00221174"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-024-04963-9","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T15:03:33Z","timestamp":1707923013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin \u03b21"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6542-6526","authenticated-orcid":false,"given":"Dagyeong","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Hye","family":"Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jeong","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hwan","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Yong","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Uk","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-5363","authenticated-orcid":false,"given":"Hoon","family":"Hur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"4963_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"4963_CR2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.4143\/crt.2022.128","volume":"54","author":"MJ Kang","year":"2022","unstructured":"Kang MJ, Won YJ, Lee JJ, Jung KW, Kim HJ, Kong HJ, Im JS, Seo HG. Community of population-based regional cancer R: cancer statistics in korea: incidence, mortality, survival, and prevalence in 2019. Cancer Res Treat. 2022;54:330\u201344.","journal-title":"Cancer Res Treat"},{"key":"4963_CR3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","volume":"64","author":"P Lauren","year":"1965","unstructured":"Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31\u201349.","journal-title":"Acta Pathol Microbiol Scand"},{"key":"4963_CR4","doi-asserted-by":"publisher","first-page":"212","DOI":"10.5230\/jgc.2010.10.4.212","volume":"10","author":"JH Jang","year":"2010","unstructured":"Jang JH, Beron RI, Ahn HS, Kong SH, Lee HJ, Kim WH, Lee KU, Yang HK. Clinicopathological features of upper third gastric cancer during a 21-year period (single center analysis). J Gastric Cancer. 2010;10:212\u20138.","journal-title":"J Gastric Cancer"},{"key":"4963_CR5","doi-asserted-by":"publisher","first-page":"148","DOI":"10.21037\/jgo.2017.01.10","volume":"8","author":"F Petrelli","year":"2017","unstructured":"Petrelli F, Berenato R, Turati L, Mennitto A, Steccanella F, Caporale M, Dallera P, de Braud F, Pezzica E, Di Bartolomeo M, et al. Prognostic value of diffuse versus intestinal histotype in patients with gastric cancer: a systematic review and meta-analysis. J Gastrointest Oncol. 2017;8:148\u201363.","journal-title":"J Gastrointest Oncol"},{"key":"4963_CR6","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1007\/s00268-002-6344-2","volume":"26","author":"D Marrelli","year":"2002","unstructured":"Marrelli D, Roviello F, de Manzoni G, Morgagni P, Di Leo A, Saragoni L, De Stefano A, Folli S, Cordiano C, Pinto E. Italian Research Group for Gastric C: different patterns of recurrence in gastric cancer depending on Lauren\u2019s histological type: longitudinal study. World J Surg. 2002;26:1160\u20135.","journal-title":"World J Surg"},{"issue":"19","key":"4963_CR7","first-page":"1","volume":"2019","author":"Guideline Committee of the Korean Gastric Cancer Association DWG, Review P","year":"2018","unstructured":"Guideline Committee of the Korean Gastric Cancer Association DWG, Review P. Korean practice guideline for gastric cancer an evidence-based, multi-disciplinary approach. J Gastric Cancer. 2018;2019(19):1\u201348.","journal-title":"J Gastric Cancer"},{"issue":"24","key":"4963_CR8","first-page":"1","volume":"2021","author":"Japanese Gastric Cancer","year":"2018","unstructured":"Japanese Gastric Cancer. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2018;2021(24):1\u201321.","journal-title":"Gastric Cancer"},{"key":"4963_CR9","first-page":"251","volume":"3","author":"B Hu","year":"2012","unstructured":"Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012;3:251\u201361.","journal-title":"J Gastrointest Oncol"},{"key":"4963_CR10","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/nm.3850","volume":"21","author":"R Cristescu","year":"2015","unstructured":"Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, Liu J, Yue YG, Wang J, Yu K, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21:449\u201356.","journal-title":"Nat Med"},{"key":"4963_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41416-018-0202-y","volume":"119","author":"N Kemi","year":"2018","unstructured":"Kemi N, Eskuri M, Herva A, Leppanen J, Huhta H, Helminen O, Saarnio J, Karttunen TJ, Kauppila JH. Tumour-stroma ratio and prognosis in gastric adenocarcinoma. Br J Cancer. 2018;119:435\u20139.","journal-title":"Br J Cancer"},{"key":"4963_CR12","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1136\/gutjnl-2011-301373","volume":"62","author":"Y Wu","year":"2013","unstructured":"Wu Y, Grabsch H, Ivanova T, Tan IB, Murray J, Ooi CH, Wright AI, West NP, Hutchins GG, Wu J, et al. Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer. Gut. 2013;62:1100\u201311.","journal-title":"Gut"},{"key":"4963_CR13","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s10120-016-0669-2","volume":"20","author":"D Lee","year":"2017","unstructured":"Lee D, Ham IH, Son SY, Han SU, Kim YB, Hur H. Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas. Gastric Cancer. 2017;20:591\u2013601.","journal-title":"Gastric Cancer"},{"key":"4963_CR14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","volume":"20","author":"E Sahai","year":"2020","unstructured":"Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20:174\u201386.","journal-title":"Nat Rev Cancer"},{"key":"4963_CR15","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nrc.2016.73","volume":"16","author":"R Kalluri","year":"2016","unstructured":"Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582\u201398.","journal-title":"Nat Rev Cancer"},{"key":"4963_CR16","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1080\/15384047.2017.1373219","volume":"18","author":"T Yang","year":"2017","unstructured":"Yang T, Chen M, Yang X, Zhang X, Zhang Z, Sun Y, Xu B, Hua J, He Z, Song Z. Down-regulation of KLF5 in cancer-associated fibroblasts inhibit gastric cancer cells progression by CCL5\/CCR5 axis. Cancer Biol Ther. 2017;18:806\u201315.","journal-title":"Cancer Biol Ther"},{"key":"4963_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1476-4598-9-13","volume":"9","author":"K Utispan","year":"2010","unstructured":"Utispan K, Thuwajit P, Abiko Y, Charngkaew K, Paupairoj A, Chau-in S, Thuwajit C. Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol Cancer. 2010;9:13.","journal-title":"Mol Cancer"},{"key":"4963_CR18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s10549-007-9725-2","volume":"110","author":"CF Singer","year":"2008","unstructured":"Singer CF, Gschwantler-Kaulich D, Fink-Retter A, Haas C, Hudelist G, Czerwenka K, Kubista E. Differential gene expression profile in breast cancer-derived stromal fibroblasts. Breast Cancer Res Treat. 2008;110:273\u201381.","journal-title":"Breast Cancer Res Treat"},{"key":"4963_CR19","doi-asserted-by":"publisher","first-page":"7366","DOI":"10.1038\/sj.onc.1208013","volume":"23","author":"H Nakagawa","year":"2004","unstructured":"Nakagawa H, Liyanarachchi S, Davuluri RV, Auer H, Martin EW Jr, de la Chapelle A, Frankel WL. Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles. Oncogene. 2004;23:7366\u201377.","journal-title":"Oncogene"},{"key":"4963_CR20","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1038\/onc.2009.463","volume":"29","author":"M Bauer","year":"2010","unstructured":"Bauer M, Su G, Casper C, He R, Rehrauer W, Friedl A. Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast. Oncogene. 2010;29:1732\u201340.","journal-title":"Oncogene"},{"key":"4963_CR21","doi-asserted-by":"publisher","first-page":"17084","DOI":"10.1074\/jbc.M301477200","volume":"278","author":"K Mukai","year":"2003","unstructured":"Mukai K, Mitani F, Nagasawa H, Suzuki R, Suzuki T, Suematsu M, Ishimura Y. An inverse correlation between expression of a preprocathepsin B-related protein with cysteine-rich sequences and steroid 11beta-hydroxylase in adrenocortical cells. J Biol Chem. 2003;278:17084\u201392.","journal-title":"J Biol Chem"},{"key":"4963_CR22","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1111\/j.1742-4658.2007.05786.x","volume":"274","author":"D Li","year":"2007","unstructured":"Li D, Mukai K, Suzuki T, Suzuki R, Yamashita S, Mitani F, Suematsu M. Adrenocortical zonation factor 1 is a novel matricellular protein promoting integrin-mediated adhesion of adrenocortical and vascular smooth muscle cells. FEBS J. 2007;274:2506\u201322.","journal-title":"FEBS J"},{"issue":"Suppl 9","key":"4963_CR23","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1186\/1471-2164-15-S9-S2","volume":"15","author":"H Umeyama","year":"2014","unstructured":"Umeyama H, Iwadate M, Taguchi YH. TINAGL1 and B3GALNT1 are potential therapy target genes to suppress metastasis in non-small cell lung cancer. BMC Genomics. 2014;15(Suppl 9):S2.","journal-title":"BMC Genomics"},{"key":"4963_CR24","doi-asserted-by":"publisher","first-page":"767","DOI":"10.2147\/CMAR.S190390","volume":"11","author":"L Sun","year":"2019","unstructured":"Sun L, Dong Z, Gu H, Guo Z, Yu Z. TINAGL1 promotes hepatocellular carcinogenesis through the activation of TGF-beta signaling-medicated VEGF expression. Cancer Manag Res. 2019;11:767\u201375.","journal-title":"Cancer Manag Res"},{"issue":"64\u201380","key":"4963_CR25","volume":"35","author":"M Shen","year":"2019","unstructured":"Shen M, Jiang YZ, Wei Y, Ell B, Sheng X, Esposito M, Kang J, Hang X, Zheng H, Rowicki M, et al. Tinagl1 suppresses triple-negative breast cancer progression and metastasis by simultaneously inhibiting integrin\/FAK and EGFR signaling. Cancer Cell. 2019;35(64\u201380): e67.","journal-title":"Cancer Cell"},{"key":"4963_CR26","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/jgh.15150","volume":"36","author":"ZG Shan","year":"2021","unstructured":"Shan ZG, Sun ZW, Zhao LQ, Gou Q, Chen ZF, Zhang JY, Chen W, Su CY, You N, Zhuang Y, Zhao YL. Upregulation of Tubulointerstitial nephritis antigen like 1 promotes gastric cancer growth and metastasis by regulating multiple matrix metallopeptidase expression. J Gastroenterol Hepatol. 2021;36:196\u2013203.","journal-title":"J Gastroenterol Hepatol"},{"key":"4963_CR27","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.matbio.2017.07.005","volume":"65","author":"V Bergmeier","year":"2018","unstructured":"Bergmeier V, Etich J, Pitzler L, Frie C, Koch M, Fischer M, Rappl G, Abken H, Tomasek JJ, Brachvogel B. Identification of a myofibroblast-specific expression signature in skin wounds. Matrix Biol. 2018;65:59\u201374.","journal-title":"Matrix Biol"},{"key":"4963_CR28","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101438RR","volume":"36","author":"WQ Tian","year":"2022","unstructured":"Tian WQ, Chen SY, Chuan FN, Zhao WR, Zhou B. Down-regulated TINAGL1 in fibroblasts impairs wound healing in diabetes. FASEB J. 2022;36: e22235.","journal-title":"FASEB J"},{"key":"4963_CR29","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1021\/pr401264n","volume":"13","author":"A Chawade","year":"2014","unstructured":"Chawade A, Alexandersson E, Levander F. Normalyzer: a tool for rapid evaluation of normalization methods for omics data sets. J Proteome Res. 2014;13:3114\u201320.","journal-title":"J Proteome Res"},{"key":"4963_CR30","doi-asserted-by":"publisher","first-page":"82538","DOI":"10.18632\/oncotarget.12757","volume":"7","author":"CG Bracamontes","year":"2016","unstructured":"Bracamontes CG, Lopez-Valdez R, Subramani R, Arumugam A, Nandy S, Rajamanickam V, Ravichandran V, Lakshmanaswamy R. The serum protein profile of early parity which induces protection against breast cancer. Oncotarget. 2016;7:82538\u201353.","journal-title":"Oncotarget"},{"key":"4963_CR31","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1002\/mc.22820","volume":"57","author":"KH Cleveland","year":"2018","unstructured":"Cleveland KH, Yeung S, Huang KM, Liang S, Andresen BT, Huang Y. Phosphoproteome profiling provides insight into the mechanism of action for carvedilol-mediated cancer prevention. Mol Carcinog. 2018;57:997\u20131007.","journal-title":"Mol Carcinog"},{"key":"4963_CR32","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1101\/gad.1758709","volume":"23","author":"KR Legate","year":"2009","unstructured":"Legate KR, Wickstrom SA, Fassler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev. 2009;23:397\u2013418.","journal-title":"Genes Dev"},{"key":"4963_CR33","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1095\/biolreprod.109.080028","volume":"82","author":"Y Tajiri","year":"2010","unstructured":"Tajiri Y, Igarashi T, Li D, Mukai K, Suematsu M, Fukui E, Yoshizawa M, Matsumoto H. Tubulointerstitial nephritis antigen-like 1 is expressed in the uterus and binds with integrins in decidualized endometrium during postimplantation in mice. Biol Reprod. 2010;82:263\u201370.","journal-title":"Biol Reprod"},{"key":"4963_CR34","doi-asserted-by":"publisher","first-page":"8487","DOI":"10.1073\/pnas.89.18.8487","volume":"89","author":"SK Hanks","year":"1992","unstructured":"Hanks SK, Calalb MB, Harper MC, Patel SK. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992;89:8487\u201391.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4963_CR35","doi-asserted-by":"publisher","first-page":"23439","DOI":"10.1016\/S0021-9258(18)35853-8","volume":"267","author":"L Kornberg","year":"1992","unstructured":"Kornberg L, Earp HS, Parsons JT, Schaller M, Juliano RL. Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. J Biol Chem. 1992;267:23439\u201342.","journal-title":"J Biol Chem"},{"key":"4963_CR36","doi-asserted-by":"publisher","first-page":"74506","DOI":"10.18632\/oncotarget.20171","volume":"8","author":"PC Chen","year":"2017","unstructured":"Chen PC, Tai HC, Lin TH, Wang SW, Lin CY, Chao CC, Yu HJ, Tsai YC, Lai YW, Lin CW, Tang CH. CCN3 promotes epithelial-mesenchymal transition in prostate cancer via FAK\/Akt\/HIF-1alpha-induced twist expression. Oncotarget. 2017;8:74506\u201318.","journal-title":"Oncotarget"},{"key":"4963_CR37","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s12935-020-01307-7","volume":"20","author":"J Li","year":"2020","unstructured":"Li J, Hao N, Han J, Zhang M, Li X, Yang N. ZKSCAN3 drives tumor metastasis via integrin beta4\/FAK\/AKT mediated epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Cell Int. 2020;20:216.","journal-title":"Cancer Cell Int"},{"key":"4963_CR38","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1083\/jcb.201105103","volume":"195","author":"XY Li","year":"2011","unstructured":"Li XY, Zhou X, Rowe RG, Hu Y, Schlaepfer DD, Ilic D, Dressler G, Park A, Guan JL, Weiss SJ. Snail1 controls epithelial-mesenchymal lineage commitment in focal adhesion kinase-null embryonic cells. J Cell Biol. 2011;195:729\u201338.","journal-title":"J Cell Biol"},{"key":"4963_CR39","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.drudis.2021.11.025","volume":"27","author":"PA Quispe","year":"2022","unstructured":"Quispe PA, Lavecchia MJ, Leon IE. Focal adhesion kinase inhibitors in the treatment of solid tumors: preclinical and clinical evidence. Drug Discov Today. 2022;27:664\u201374.","journal-title":"Drug Discov Today"},{"key":"4963_CR40","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1111\/cbdd.13808","volume":"97","author":"A Chauhan","year":"2021","unstructured":"Chauhan A, Khan T. Focal adhesion kinase-An emerging viable target in cancer and development of focal adhesion kinase inhibitors. Chem Biol Drug Des. 2021;97:774\u201394.","journal-title":"Chem Biol Drug Des"},{"key":"4963_CR41","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/onc.2017.363","volume":"37","author":"L Gan","year":"2018","unstructured":"Gan L, Meng J, Xu M, Liu M, Qi Y, Tan C, Wang Y, Zhang P, Weng W, Sheng W, et al. Extracellular matrix protein 1 promotes cell metastasis and glucose metabolism by inducing integrin beta4\/FAK\/SOX2\/HIF-1alpha signaling pathway in gastric cancer. Oncogene. 2018;37:744\u201355.","journal-title":"Oncogene"},{"key":"4963_CR42","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1002\/ijc.30801","volume":"141","author":"X Wang","year":"2017","unstructured":"Wang X, Zhou Q, Yu Z, Wu X, Chen X, Li J, Li C, Yan M, Zhu Z, Liu B, Su L. Cancer-associated fibroblast-derived Lumican promotes gastric cancer progression via the integrin beta1-FAK signaling pathway. Int J Cancer. 2017;141:998\u20131010.","journal-title":"Int J Cancer"},{"key":"4963_CR43","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s11523-018-00617-1","volume":"14","author":"MJA de Jonge","year":"2019","unstructured":"de Jonge MJA, Steeghs N, Lolkema MP, Hotte SJ, Hirte HW, van der Biessen DAJ, Abdul Razak AR, De Vos F, Verheijen RB, Schnell D, et al. Phase I study of BI 853520, an inhibitor of focal adhesion kinase, in patients with advanced or metastatic nonhematologic malignancies. Target Oncol. 2019;14:43\u201355.","journal-title":"Target Oncol"},{"key":"4963_CR44","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.lungcan.2019.10.033","volume":"139","author":"DE Gerber","year":"2020","unstructured":"Gerber DE, Camidge DR, Morgensztern D, Cetnar J, Kelly RJ, Ramalingam SS, Spigel DR, Jeong W, Scaglioni PP, Zhang S, et al. Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer. Lung Cancer. 2020;139:60\u20137.","journal-title":"Lung Cancer"},{"key":"4963_CR45","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/s41416-019-0452-3","volume":"120","author":"G Mak","year":"2019","unstructured":"Mak G, Soria JC, Blagden SP, Plummer R, Fleming RA, Nebot N, Zhang J, Mazumdar J, Rogan D, Gazzah A, et al. A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours. Br J Cancer. 2019;120:975\u201381.","journal-title":"Br J Cancer"},{"issue":"946\u2013957","key":"4963_CR46","volume":"156","author":"WJ Sandborn","year":"2019","unstructured":"Sandborn WJ, Cyrille M, Hansen MB, Feagan BG, Loftus EV Jr, Rogler G, Vermeire S, Cruz ML, Yang J, Boedigheimer MJ, et al. Efficacy and safety of abrilumab in a randomized, placebo-controlled trial for moderate-to-severe ulcerative colitis. Gastroenterology. 2019;156(946\u2013957): e918.","journal-title":"Gastroenterology"},{"key":"4963_CR47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S2468-1253(22)00303-X","volume":"8","author":"WJ Sandborn","year":"2023","unstructured":"Sandborn WJ, Panes J, Danese S, Sharafali Z, Hassanali A, Jacob-Moffatt R, Eden C, Daperno M, Valentine JF, Laharie D, et al. Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn\u2019s disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2023;8:43\u201355.","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"4963_CR48","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12931-020-01339-7","volume":"21","author":"TM Maher","year":"2020","unstructured":"Maher TM, Simpson JK, Porter JC, Wilson FJ, Chan R, Eames R, Cui Y, Siederer S, Parry S, Kenny J, et al. A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled alphavbeta6 integrin inhibitor. Respir Res. 2020;21:75.","journal-title":"Respir Res"},{"key":"4963_CR49","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41571-021-00546-5","volume":"18","author":"Y Chen","year":"2021","unstructured":"Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 2021;18:792\u2013804.","journal-title":"Nat Rev Clin Oncol"},{"key":"4963_CR50","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1158\/1541-7786.MCR-21-0282","volume":"20","author":"T Simon","year":"2022","unstructured":"Simon T, Salhia B. Cancer-associated fibroblast subpopulations with diverse and dynamic roles in the tumor microenvironment. Mol Cancer Res. 2022;20:183\u201392.","journal-title":"Mol Cancer Res"},{"key":"4963_CR51","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","volume":"9","author":"E Elyada","year":"2019","unstructured":"Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET, Burkhart RA, Teinor JA, Belleau P, Biffi G, Lucito MS, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 2019;9:1102\u201323.","journal-title":"Cancer Discov"},{"key":"4963_CR52","doi-asserted-by":"publisher","first-page":"6529","DOI":"10.1158\/1078-0432.CCR-21-0792","volume":"27","author":"HY Jeong","year":"2021","unstructured":"Jeong HY, Ham IH, Lee SH, Ryu D, Son SY, Han SU, Kim TM, Hur H. Spatially distinct reprogramming of the tumor microenvironment based on tumor invasion in diffuse-type gastric cancers. Clin Cancer Res. 2021;27:6529\u201342.","journal-title":"Clin Cancer Res"},{"key":"4963_CR53","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/bjc.2011.330","volume":"105","author":"Y Fuyuhiro","year":"2011","unstructured":"Fuyuhiro Y, Yashiro M, Noda S, Kashiwagi S, Matsuoka J, Doi Y, Kato Y, Hasegawa T, Sawada T, Hirakawa K. Upregulation of cancer-associated myofibroblasts by TGF-beta from scirrhous gastric carcinoma cells. Br J Cancer. 2011;105:996\u20131001.","journal-title":"Br J Cancer"},{"key":"4963_CR54","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1186\/s12967-021-03012-z","volume":"19","author":"X Liu","year":"2021","unstructured":"Liu X, Yao L, Qu J, Liu L, Lu N, Wang J, Zhang J. Cancer-associated fibroblast infiltration in gastric cancer: the discrepancy in subtypes pathways and immunosuppression. J Transl Med. 2021;19:325.","journal-title":"J Transl Med"},{"key":"4963_CR55","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1158\/1078-0432.CCR-21-3570","volume":"28","author":"A Obradovic","year":"2022","unstructured":"Obradovic A, Graves D, Korrer M, Wang Y, Roy S, Naveed A, Xu Y, Luginbuhl A, Curry J, Gibson M, et al. Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer. Clin Cancer Res. 2022;28:2094\u2013109.","journal-title":"Clin Cancer Res"},{"key":"4963_CR56","doi-asserted-by":"publisher","first-page":"167","DOI":"10.4143\/crt.2022.094","volume":"55","author":"D Lee","year":"2023","unstructured":"Lee D, Choi J, Oh HJ, Ham IH, Lee SH, Nomura S, Han SU, Hur H. Molecular and immune profiling of syngeneic mouse models predict response to immune checkpoint inhibitors in gastric cancer. Cancer Res Treat. 2023;55:167\u201378.","journal-title":"Cancer Res Treat"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-024-04963-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-024-04963-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-024-04963-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T23:15:04Z","timestamp":1708298104000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-024-04963-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4963"],"URL":"https:\/\/doi.org\/10.1186\/s12967-024-04963-9","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,14]]},"assertion":[{"value":"13 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal care and handling were carried out in accordance with the guidelines of the Ajou University School of Medicine Institutional Animal Care and Use Committee (IACUC). All animal experiments were approved by the Animal Research Committee of the institution (2015-0069). All procedures were conducted in accordance with the Declaration of Helsinki guidelines and approved AJOU University Institutional Review Board (AJOUIRB-GEN-2014-376), and informed consent or an appropriate substitute for it was obtained from all patients included in the study.","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 that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"154"}}