{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:26:05Z","timestamp":1783542365281,"version":"3.55.0"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018921","name":"Yulin Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024-SF-024"],"award-info":[{"award-number":["2024-SF-024"]}],"id":[{"id":"10.13039\/100018921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2023-JC-QN-0840"],"award-info":[{"award-number":["2023-JC-QN-0840"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.canlet.2026.218306","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:56:09Z","timestamp":1770882969000},"page":"218306","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["PPP4C restores YAP1 activity by modulating MST4 phosphorylation to enhance immunosuppression and augment tumor growth in non-small cell lung cancer"],"prefix":"10.1016","volume":"644","author":[{"given":"Zhengshui","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changchun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangzhang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiantao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5768-6746","authenticated-orcid":false,"given":"Shiyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.canlet.2026.218306_bib1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"issue":"148","key":"10.1016\/j.canlet.2026.218306_bib2","first-page":"167","article-title":"Molecular diagnostics and targeted therapies in non-small cell lung cancer (NSCLC): an update","volume":"27","author":"Jonna","year":"2019","journal-title":"Discov. Med."},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib3","doi-asserted-by":"crossref","first-page":"8155","DOI":"10.18632\/aging.202625","article-title":"FAM72 serves as a biomarker of poor prognosis in human lung adenocarcinoma","volume":"13","author":"Yu","year":"2021","journal-title":"Aging (Albany NY)"},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/nyas.14526","article-title":"Frontiers in cancer immunotherapy-a symposium report","volume":"1489","author":"Cable","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"4","key":"10.1016\/j.canlet.2026.218306_bib5","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"issue":"8","key":"10.1016\/j.canlet.2026.218306_bib6","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.drudis.2017.05.016","article-title":"Understanding the checkpoint blockade in lung cancer immunotherapy","volume":"22","author":"Dal Bello","year":"2017","journal-title":"Drug Discov. Today"},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40425-018-0382-2","article-title":"The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)","volume":"6","author":"Brahmer","year":"2018","journal-title":"J. Immunother. Cancer"},{"issue":"7","key":"10.1016\/j.canlet.2026.218306_bib8","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1056\/NEJMoa1916623","article-title":"The effect of advances in lung-cancer treatment on population mortality","volume":"383","author":"Howlader","year":"2020","journal-title":"N. Engl. J. Med."},{"issue":"24","key":"10.1016\/j.canlet.2026.218306_bib9","doi-asserted-by":"crossref","DOI":"10.3390\/cells11244057","article-title":"MST4: a potential oncogene and therapeutic target in breast cancer","volume":"11","author":"Arora","year":"2022","journal-title":"Cells"},{"issue":"25","key":"10.1016\/j.canlet.2026.218306_bib10","doi-asserted-by":"crossref","first-page":"22439","DOI":"10.1074\/jbc.M009323200","article-title":"Cloning and characterization of MST4, a novel Ste20-like kinase","volume":"276","author":"Qian","year":"2001","journal-title":"J. Biol. Chem."},{"issue":"28","key":"10.1016\/j.canlet.2026.218306_bib11","doi-asserted-by":"crossref","first-page":"25056","DOI":"10.1074\/jbc.M110.213777","article-title":"CCM3\/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization","volume":"286","author":"Ceccarelli","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"45","key":"10.1016\/j.canlet.2026.218306_bib12","doi-asserted-by":"crossref","first-page":"6559","DOI":"10.1038\/sj.onc.1204818","article-title":"MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway","volume":"20","author":"Lin","year":"2001","journal-title":"Oncogene"},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib13","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1091\/mbc.e06-07-0608","article-title":"PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway","volume":"18","author":"Ma","year":"2007","journal-title":"Mol. Biol. Cell"},{"issue":"47","key":"10.1016\/j.canlet.2026.218306_bib14","doi-asserted-by":"crossref","first-page":"28272","DOI":"10.1074\/jbc.M115.668855","article-title":"Cell polarity kinase MST4 cooperates with cAMP-dependent kinase to orchestrate histamine-stimulated acid secretion in gastric parietal cells","volume":"290","author":"Jiang","year":"2015","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e16735","article-title":"MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy","volume":"9","author":"Liu","year":"2023","journal-title":"Heliyon"},{"issue":"2","key":"10.1016\/j.canlet.2026.218306_bib16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3892\/ijo.2014.2455","article-title":"MST4 promotes hepatocellular carcinoma epithelial-mesenchymal transition and metastasis via activation of the p-ERK pathway","volume":"45","author":"Lin","year":"2014","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.canlet.2026.218306_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2023.216183","article-title":"The mammalian Sterile 20-like kinase 4 (MST4) signaling in tumor progression: implications for therapy","volume":"563","author":"Getu","year":"2023","journal-title":"Cancer Lett."},{"issue":"15","key":"10.1016\/j.canlet.2026.218306_bib18","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.7150\/jca.60008","article-title":"MST4 negatively regulates the EMT, invasion and metastasis of HCC cells by inactivating PI3K\/AKT\/Snail1 axis","volume":"12","author":"Dian","year":"2021","journal-title":"J. Cancer"},{"key":"10.1016\/j.canlet.2026.218306_bib19","doi-asserted-by":"crossref","first-page":"8357","DOI":"10.1038\/ncomms9357","article-title":"MAP4K family kinases act in parallel to MST1\/2 to activate LATS1\/2 in the hippo pathway","volume":"6","author":"Meng","year":"2015","journal-title":"Nat. Commun."},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib20","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.devcel.2015.08.014","article-title":"Identification of Happyhour\/MAP4K as alternative Hpo\/Mst-like kinases in the Hippo kinase Cascade","volume":"34","author":"Zheng","year":"2015","journal-title":"Dev. Cell"},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.274027.115","article-title":"Mechanisms of Hippo pathway regulation","volume":"30","author":"Meng","year":"2016","journal-title":"Genes Dev."},{"issue":"35","key":"10.1016\/j.canlet.2026.218306_bib22","article-title":"TRIM65\/NF2\/YAP1 signaling coordinately Orchestrates metabolic and immune advantages in hepatocellular carcinoma","volume":"11","author":"Bian","year":"2024","journal-title":"Adv. Sci. (Weinh.)"},{"issue":"2","key":"10.1016\/j.canlet.2026.218306_bib23","doi-asserted-by":"crossref","DOI":"10.1172\/JCI171164","article-title":"YAP1 induces bladder cancer progression and promotes immune evasion through IL-6\/STAT3 pathway and CXCL deregulation","volume":"135","author":"Sadhukhan","year":"2024","journal-title":"J. Clin. Investig."},{"issue":"8","key":"10.1016\/j.canlet.2026.218306_bib24","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41419-024-07017-6","article-title":"Radiation-induced YAP\/TEAD4 binding confers non-small cell lung cancer radioresistance via promoting NRP1 transcription","volume":"15","author":"Wang","year":"2024","journal-title":"Cell Death Dis."},{"issue":"8","key":"10.1016\/j.canlet.2026.218306_bib25","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.7150\/ijbs.79965","article-title":"YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR\/MAPK pathway and abrogating autophagy in non-small cell lung cancer","volume":"19","author":"Ning","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.canlet.2026.218306_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2025.101245","article-title":"Long non-coding RNA LRTOR drives osimertinib resistance in non-small cell lung cancer by boosting YAP positive feedback loop","volume":"83","author":"Miao","year":"2025","journal-title":"Drug Resist. Updates"},{"issue":"20","key":"10.1016\/j.canlet.2026.218306_bib27","doi-asserted-by":"crossref","first-page":"28976","DOI":"10.18632\/oncotarget.6721","article-title":"Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells","volume":"7","author":"Cheng","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2026.218306_bib28","article-title":"YAP1 as a novel negative biomarker of immune checkpoint inhibitors for EGFR-mutant non-small-cell lung cancer","author":"Li","year":"2023","journal-title":"Cancer Res. J."},{"issue":"9","key":"10.1016\/j.canlet.2026.218306_bib29","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/ncb3216","article-title":"Genome-wide association between YAP\/TAZ\/TEAD and AP-1 at enhancers drives oncogenic growth","volume":"17","author":"Zanconato","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.canlet.2026.218306_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217467","article-title":"Targeting YAP\/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma","volume":"612","author":"Sato","year":"2025","journal-title":"Cancer Lett."},{"issue":"19","key":"10.1016\/j.canlet.2026.218306_bib31","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1016\/j.febslet.2008.07.014","article-title":"Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6","volume":"582","author":"Chen","year":"2008","journal-title":"FEBS Lett."},{"key":"10.1016\/j.canlet.2026.218306_bib32","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/5550498","article-title":"Protein phosphatase 4 promotes hepatocyte lipoapoptosis by regulating RAC1\/MLK3\/JNK pathway","volume":"2021","author":"Huang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"9","key":"10.1016\/j.canlet.2026.218306_bib33","doi-asserted-by":"crossref","first-page":"eade3760","DOI":"10.1126\/sciadv.ade3760","article-title":"ATM-SPARK: a GFP phase separation-based activity reporter of ATM","volume":"9","author":"Li","year":"2023","journal-title":"Sci. Adv."},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12943-019-1102-3","article-title":"Harnessing tumor-associated macrophages as aids for cancer immunotherapy","volume":"18","author":"Li","year":"2019","journal-title":"Mol. Cancer"},{"issue":"12","key":"10.1016\/j.canlet.2026.218306_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22126536","article-title":"TMB in NSCLC: a broken dream?","volume":"22","author":"Bravaccini","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"12","key":"10.1016\/j.canlet.2026.218306_bib36","first-page":"3356","article-title":"The Ste20 kinase MST4 plays a role in prostate cancer progression","volume":"63","author":"Sung","year":"2003","journal-title":"Cancer Res."},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib37","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1083\/jcb.201507005","article-title":"MST kinases in development and disease","volume":"210","author":"Thompson","year":"2015","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.canlet.2026.218306_bib38","doi-asserted-by":"crossref","first-page":"9353","DOI":"10.2147\/CMAR.S219689","article-title":"MST4 predicts poor prognosis and promotes metastasis by facilitating epithelial-mesenchymal transition in gastric cancer","volume":"11","author":"Li","year":"2019","journal-title":"Cancer Manag. Res."},{"issue":"17","key":"10.1016\/j.canlet.2026.218306_bib39","doi-asserted-by":"crossref","first-page":"5106","DOI":"10.7150\/jca.45822","article-title":"MST4 inhibits human hepatocellular carcinoma cell proliferation and induces cell cycle arrest via suppression of PI3K\/AKT pathway","volume":"11","author":"Hao","year":"2020","journal-title":"J. Cancer"},{"issue":"6","key":"10.1016\/j.canlet.2026.218306_bib40","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191817","article-title":"MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway","volume":"217","author":"An","year":"2020","journal-title":"J. Exp. Med."},{"issue":"12","key":"10.1016\/j.canlet.2026.218306_bib41","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/s41423-023-01089-8","article-title":"MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages","volume":"20","author":"Cao","year":"2023","journal-title":"Cell. Mol. Immunol."},{"issue":"4","key":"10.1016\/j.canlet.2026.218306_bib42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","article-title":"CD8(+) T cell states in human cancer: insights from single-cell analysis","volume":"20","author":"van der Leun","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2026.218306_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/froh.2020.585710","article-title":"Hypoxic transformation of immune cell metabolism within the microenvironment of oral cancers","volume":"1","author":"Chaudhary","year":"2020","journal-title":"Front. Oral Health"},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib44","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.gendis.2019.12.004","article-title":"Immune checkpoint: the novel target for antitumor therapy","volume":"8","author":"Jiang","year":"2021","journal-title":"Genes Dis."},{"key":"10.1016\/j.canlet.2026.218306_bib45","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ydbio.2020.12.018","article-title":"YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance","volume":"475","author":"Szulzewsky","year":"2021","journal-title":"Dev. Biol."},{"issue":"9","key":"10.1016\/j.canlet.2026.218306_bib46","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/s41419-023-06053-y","article-title":"YAP1 expression is associated with survival and immunosuppression in small cell lung cancer","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.canlet.2026.218306_bib47","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fcell.2018.00030","article-title":"Coordination of protein kinase and phosphoprotein phosphatase activities in mitosis","volume":"6","author":"Nasa","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib48","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20203282","article-title":"The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer","volume":"41","author":"Hang","year":"2021","journal-title":"Biosci. Rep."},{"issue":"1","key":"10.1016\/j.canlet.2026.218306_bib49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10238-024-01356-6","article-title":"High PPP4C expression predicts poor prognosis in diffuse large B-cell lymphoma","volume":"24","author":"Hui","year":"2024","journal-title":"Clin. Exp. Med."},{"issue":"12","key":"10.1016\/j.canlet.2026.218306_bib50","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-005026","article-title":"PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling","volume":"10","author":"Raja","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218306_bib51","article-title":"Comprehensive analysis of PPP4C's impact on prognosis, immune microenvironment, and immunotherapy response in lung adenocarcinoma using single-cell sequencing and multi-omics","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Immunol."}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526000698?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526000698?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:41:14Z","timestamp":1783539674000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526000698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":51,"alternative-id":["S0304383526000698"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218306","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PPP4C restores YAP1 activity by modulating MST4 phosphorylation to enhance immunosuppression and augment tumor growth in non-small cell lung cancer","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218306","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"218306"}}