{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:15:49Z","timestamp":1780046149207,"version":"3.53.1"},"reference-count":40,"publisher":"China Science Publishing & Media Ltd.","content-domain":{"domain":["engine.scichina.com"],"crossmark-restriction":false},"short-container-title":["ABBS"],"published-print":{"date-parts":[[2026,5,1]]},"DOI":"10.3724\/abbs.2026095","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T02:38:21Z","timestamp":1779071901000},"update-policy":"https:\/\/doi.org\/10.1360\/scp-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["MAL2 drives hepatocellular carcinoma progression by recruiting regulatory T cells via CCL22 and inducing the immunosuppressive microenvironment"],"prefix":"10.3724","author":[{"given":"Qian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lantian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2026","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"CITATION1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"Sung H","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: 209-249.","journal-title":"CA Cancer J Clin"},{"key":"CITATION2","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.jhep.2025.06.034","volume":"83","author":"Chen Y","year":"2025","unstructured":"Chen Y, Lee D, Kwan KKL, Wu M, Wang G, Zhang MS, Deng H. Mevalonate pathway promotes liver cancer by suppressing ferroptosis through CoQ10 production and selenocysteine-tRNA modification. J Hepatol, 2025, 83: 1338-1352.","journal-title":"J Hepatol"},{"key":"CITATION3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1053\/jhep.2002.32089","volume":"35","author":"Bruix J","year":"2002","unstructured":"Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology, 2002, 35: 519-524.","journal-title":"Hepatology"},{"key":"CITATION4","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.jhep.2024.08.028","volume":"82","author":"Sangro B","year":"2025","unstructured":"Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P. EASL clinical practice guidelines on the management of hepatocellular carcinoma. J Hepatol, 2025, 82: 315-374.","journal-title":"J Hepatol"},{"key":"CITATION5","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.cell.2019.08.052","volume":"179","author":"Gao Q","year":"2019","unstructured":"Gao Q, Zhu H, Dong L, Shi W, Chen R, Song Z, Huang C. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma. Cell, 2019, 179: 561-577.e22.","journal-title":"Cell"},{"key":"CITATION6","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.cell.2020.11.041","volume":"184","author":"Sun Y","year":"2021","unstructured":"Sun Y, Wu L, Zhong Y, Zhou K, Hou Y, Wang Z, Zhang Z. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell, 2021, 184: 404-421.e16.","journal-title":"Cell"},{"key":"CITATION7","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.devcel.2010.04.001","volume":"18","author":"Madrid R","year":"2010","unstructured":"Madrid R, Aranda JF, Rodr\u00edguez-Fraticelli AE, Ventimiglia L, Andr\u00e9s-Delgado L, Shehata M, Fanayan S. The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2. Dev Cell, 2010, 18: 814-827.","journal-title":"Dev Cell"},{"key":"CITATION8","doi-asserted-by":"publisher","first-page":"e140837","DOI":"10.1172\/JCI140837","volume":"131","author":"Fang Y","year":"2021","unstructured":"Fang Y, Wang L, Wan C, Sun Y, Van der Jeught K, Zhou Z, Dong T. MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation. J Clin Invest, 2021, 131: e140837.","journal-title":"J Clin Invest"},{"key":"CITATION9","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.surg.2013.03.010","volume":"154","author":"Eguchi D","year":"2013","unstructured":"Eguchi D, Ohuchida K, Kozono S, Ikenaga N, Shindo K, Cui L, Fujiwara K. MAL2 expression predicts distant metastasis and short survival in pancreatic cancer. Surgery, 2013, 154: 573-582.","journal-title":"Surgery"},{"key":"CITATION10","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Hao Y","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck Iii WM, Zheng S, Butler A, Lee MJ. Integrated analysis of multimodal single-cell data. Cell, 2021, 184: 3573-3587.e29.","journal-title":"Cell"},{"key":"CITATION11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"McGinnis CS","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst, 2019, 8: 329-337.e4.","journal-title":"Cell Syst"},{"key":"CITATION12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13059-020-1950-6","volume":"21","author":"Yang S","year":"2020","unstructured":"Yang S, Corbett SE, Koga Y, Wang Z, Johnson WE, Yajima M, Campbell JD. Decontamination of ambient RNA in single-cell RNA-seq with DecontX. Genome Biol, 2020, 21: 57.","journal-title":"Genome Biol"},{"key":"CITATION13","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"Korsunsky I","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y. Fast, sensitive and accurate integration of single-cell data with harmony. Nat Methods, 2019, 16: 1289-1296.","journal-title":"Nat Methods"},{"key":"CITATION14","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1038\/s41467-020-16904-3","volume":"11","author":"Liu B","year":"2020","unstructured":"Liu B, Li C, Li Z, Wang D, Ren X, Zhang Z. An entropy-based metric for assessing the purity of single cell populations. Nat Commun, 2020, 11: 3155.","journal-title":"Nat Commun"},{"key":"CITATION15","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.cell.2019.10.003","volume":"179","author":"Zhang Q","year":"2019","unstructured":"Zhang Q, He Y, Luo N, Patel SJ, Han Y, Gao R, Modak M. Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell, 2019, 179: 829-845.e20.","journal-title":"Cell"},{"key":"CITATION16","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"Wu T","year":"2021","unstructured":"Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation, 2021, 2: 100141.","journal-title":"Innovation"},{"key":"CITATION17","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41419-024-06775-7","volume":"15","author":"Huang T","year":"2024","unstructured":"Huang T, Cao H, Liu C, Sun X, Dai S, Liu L, Wang Y. MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR\/SREBP-1 pathway based on single-cell RNA sequencing. Cell Death Dis, 2024, 15: 411.","journal-title":"Cell Death Dis"},{"key":"CITATION18","doi-asserted-by":"publisher","first-page":"5280","DOI":"10.3390\/cancers15215280","volume":"15","author":"To JC","year":"2023","unstructured":"To JC, Gao S, Li XX, Zhao Y, Keng VW. Sorafenib resistance contributed by IL7 and MAL2 in hepatocellular carcinoma can be overcome by autophagy-inducing stapled peptides. Cancers, 2023, 15: 5280.","journal-title":"Cancers"},{"key":"CITATION19","doi-asserted-by":"publisher","first-page":"422","DOI":"10.3390\/cancers12020422","volume":"12","author":"L\u00f3pez-Coral A","year":"2020","unstructured":"L\u00f3pez-Coral A, del Vecchio GJ, Chahine JJ, Kallakury BV, Tuma PL. MAL2-induced actin-based protrusion formation is anti-oncogenic in hepatocellular carcinoma. Cancers, 2020, 12: 422.","journal-title":"Cancers"},{"key":"CITATION20","doi-asserted-by":"publisher","first-page":"e0178515","DOI":"10.1371\/journal.pone.0178515","volume":"12","author":"Li J","year":"2017","unstructured":"Li J, Li Y, Liu H, Liu Y, Cui B, Ahmad A. The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis. PLoS One, 2017, 12: e0178515.","journal-title":"PLoS One"},{"key":"CITATION21","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.biopha.2018.06.050","volume":"105","author":"Gao X","year":"2018","unstructured":"Gao X, Chen Z, Li A, Zhang X, Cai X. MiR-129 regulates growth and invasion by targeting MAL2 in papillary thyroid carcinoma. Biomed Pharmacother, 2018, 105: 1072-1078.","journal-title":"Biomed Pharmacother"},{"key":"CITATION22","doi-asserted-by":"publisher","first-page":"7919","DOI":"10.1038\/s41467-025-62934-0","volume":"16","author":"Sequera C","year":"2025","unstructured":"Sequera C, Grattarola M, Cannet F, Dobric A, Michea Veloso P, Methia M, Richelme S. The HDAC inhibitor romidepsin renders liver cancer vulnerable to RTK targeting and immunologically active. Nat Commun, 2025, 16: 7919.","journal-title":"Nat Commun"},{"key":"CITATION23","doi-asserted-by":"publisher","first-page":"110160","DOI":"10.1016\/j.celrep.2021.110160","volume":"37","author":"Jeong J","year":"2021","unstructured":"Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Rep, 2021, 37: 110160.","journal-title":"Cell Rep"},{"key":"CITATION24","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12935-023-02993-9","volume":"23","author":"An L","year":"2023","unstructured":"An L, Gong H, Yu X, Zhang W, Liu X, Yang X, Shu L. Downregulation of MAL2 inhibits breast cancer progression through regulating \u03b2-catenin\/c-Myc axis. Cancer Cell Int, 2023, 23: 144.","journal-title":"Cancer Cell Int"},{"key":"CITATION25","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.3802\/jgo.2025.36.e11","volume":"36","author":"Cao Y","year":"2025","unstructured":"Cao Y, Peng Y, Tang Y. ATF1 regulates MAL2 expression through inhibition of miR-630 to mediate the EMT process that promotes cervical cancer cell development and metastasis. J Gynecol Oncol, 2025, 36: e11.","journal-title":"J Gynecol Oncol"},{"key":"CITATION26","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.62347\/BEUV4081","volume":"14","author":"Bi C","year":"2024","unstructured":"Bi C. Extracellular putrescine can augment the epithelial-mesenchymal transition of gastric cancer cells by promoting MAL2 expression by elevating H3K27ac in its promoter region. Am J Cancer Res, 2024, 14: 2805-2822.","journal-title":"Am J Cancer Res"},{"key":"CITATION27","doi-asserted-by":"crossref","unstructured":"Sherwin RE, McGlinch EB, Barry MA, Padilla C, Montonye DR, Evans CH,                         et al. Aav-mediated,                         in vivo gene delivery to the rotator cuff.                                                      European Cells and Materials                          2023, 46: 154\u2013170.","DOI":"10.22203\/eCM.v046a08"},{"key":"CITATION28","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.ccell.2023.02.014","volume":"41","author":"Tay C","year":"2023","unstructured":"Tay C, Tanaka A, Sakaguchi S. Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy. Cancer Cell, 2023, 41: 450-465.","journal-title":"Cancer Cell"},{"key":"CITATION29","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/ni.3522","volume":"17","author":"Wyss L","year":"2016","unstructured":"Wyss L, Stadinski BD, King CG, Schallenberg S, McCarthy NI, Lee JY, Kretschmer K. Affinity for self antigen selects Treg cells with distinct functional properties. Nat Immunol, 2016, 17: 1093-1101.","journal-title":"Nat Immunol"},{"key":"CITATION30","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.ccell.2025.01.001","volume":"43","author":"Guo X","year":"2025","unstructured":"Guo X, Nie H, Zhang W, Li J, Ge J, Xie B, Hu W. Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer. Cancer Cell, 2025, 43: 248-268.e9.","journal-title":"Cancer Cell"},{"key":"CITATION31","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.jhep.2021.07.032","volume":"75","author":"Wang H","year":"2021","unstructured":"Wang H, Zhang H, Wang Y, Brown ZJ, Xia Y, Huang Z, Shen C. Regulatory T-cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis. J Hepatol, 2021, 75: 1271-1283.","journal-title":"J Hepatol"},{"key":"CITATION32","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s12072-020-10014-4","volume":"14","author":"Park H","year":"2020","unstructured":"Park H, Jung JH, Jung MK, Shin EC, Ro SW, Park JH, Kim DY. Effects of transarterial chemoembolization on regulatory T cell and its subpopulations in patients with hepatocellular carcinoma. Hepatol Int, 2020, 14: 249-258.","journal-title":"Hepatol Int"},{"key":"CITATION33","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41577-025-01149-2","volume":"25","author":"Piao W","year":"2025","unstructured":"Piao W, Lee ZL, Zapas G, Wu L, Jewell CM, Abdi R, Bromberg JS. Regulatory T cell and endothelial cell crosstalk. Nat Rev Immunol, 2025, 25: 588-607.","journal-title":"Nat Rev Immunol"},{"key":"CITATION34","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nm1093","volume":"10","author":"Curiel TJ","year":"2004","unstructured":"Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med, 2004, 10: 942-949.","journal-title":"Nat Med"},{"key":"CITATION35","doi-asserted-by":"publisher","first-page":"6143","DOI":"10.1158\/0008-5472.CAN-11-0573","volume":"71","author":"Faget J","year":"2011","unstructured":"Faget J, Biota C, Bachelot T, Gobert M, Treilleux I, Goutagny N, Durand I. Early detection of tumor cells by innate immune cells leads to Treg recruitment through CCL22 production by tumor cells. Cancer Res, 2011, 71: 6143-6152.","journal-title":"Cancer Res"},{"key":"CITATION36","doi-asserted-by":"publisher","first-page":"6230","DOI":"10.1158\/0008-5472.CAN-16-0618","volume":"76","author":"Klarquist J","year":"2016","unstructured":"Klarquist J, Tobin K, Farhangi Oskuei P, Henning SW, Fernandez MF, Dellacecca ER, Navarro FC. Ccl22 diverts T regulatory cells and controls the growth of melanoma. Cancer Res, 2016, 76: 6230-6240.","journal-title":"Cancer Res"},{"key":"CITATION37","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/hon.2993","volume":"41","author":"Li X","year":"2023","unstructured":"Li X, Liu M, Shi Q, Fang Y, Fu D, Shen Z, Yi H. Elevated serum IL-13 level is associated with increased Treg cells in tumor microenvironment and disease progression of diffuse large B-cell lymphoma. Hematological Oncol, 2023, 41: 230-238.","journal-title":"Hematological Oncol"},{"key":"CITATION38","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jhep.2010.07.014","volume":"54","author":"Riezu-Boj JI","year":"2011","unstructured":"Riezu-Boj JI, Larrea E, Aldabe R, Guembe L, Casares N, Galeano E, Echeverria I. Hepatitis C virus induces the expression of CCL17 and CCL22 chemokines that attract regulatory T cells to the site of infection. J Hepatol, 2011, 54: 422-431.","journal-title":"J Hepatol"},{"key":"CITATION39","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1053\/j.gastro.2016.02.040","volume":"150","author":"Zhou SL","year":"2016","unstructured":"Zhou SL, Zhou ZJ, Hu ZQ, Huang XW, Wang Z, Chen EB, Fan J. Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology, 2016, 150: 1646-1658.e17.","journal-title":"Gastroenterology"},{"key":"CITATION40","doi-asserted-by":"publisher","first-page":"e180679","DOI":"10.1172\/JCI180679","volume":"135","author":"Chen R","year":"2025","unstructured":"Chen R, Zhang X, Li B, Tonetti MS, Yang Y, Li Y, Liu B. Progranulin-dependent repair function of regulatory T cells drives bone-fracture healing. J Clin Invest, 2025, 135: e180679.","journal-title":"J Clin Invest"}],"container-title":["Acta Biochimica et Biophysica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.sciengine.com\/doi\/pdf\/8A7253F22D4540808E9EBF1A446DD644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.sciengine.com\/doi\/10.3724\/abbs.2026095","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.sciengine.com\/doi\/pdf\/8A7253F22D4540808E9EBF1A446DD644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:37:50Z","timestamp":1780043870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.sciengine.com\/doi\/10.3724\/abbs.2026095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":40,"URL":"https:\/\/doi.org\/10.3724\/abbs.2026095","relation":{},"ISSN":["1672-9145"],"issn-type":[{"value":"1672-9145","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5,1]]}}}