{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:26:49Z","timestamp":1781634409424,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ22H160024"],"award-info":[{"award-number":["LQ22H160024"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H160011"],"award-info":[{"award-number":["LY21H160011"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of AT\u2010interacting domain\u2010rich protein 1A (<jats:italic>ARID1A<\/jats:italic>) frequently occurs in human malignancies including lung cancer. The biological consequence of <jats:italic>ARID1A<\/jats:italic> mutation in lung cancer is not fully understood. This study was designed to determine the effect of <jats:italic>ARID1A<\/jats:italic>\u2010depleted lung cancer cells on fibroblast activation. Conditioned media was collected from <jats:italic>ARID1A<\/jats:italic>\u2010depleted lung cancer cells and employed to treat lung fibroblasts. The proliferation and migration of lung fibroblasts were investigated. The secretory genes were profiled in lung cancer cells upon <jats:italic>ARID1A<\/jats:italic> knockdown. Antibody\u2010based neutralization was utilized to confirm their role in mediating the cross\u2010talk between lung cancer cells and fibroblasts. NOD\u2010SCID\u2010IL2RgammaC\u2010null (NSG) mice received tumor tissues from patients with ARID1A\u2010mutated lung cancer to establish patient\u2010derived xenograft (PDX) models. Notably, <jats:italic>ARID1A<\/jats:italic>\u2010depleted lung cancer cells promoted the proliferation and migration of lung fibroblasts. Mechanistically, <jats:italic>ARID1A<\/jats:italic> depletion augmented the expression and secretion of prolyl 4\u2010hydroxylase beta (P4HB) in lung cancer cells, which induced the activation of lung fibroblasts through the \u03b2\u2010catenin signaling pathway. P4HB\u2010activated lung fibroblasts promoted the proliferation, invasion, and chemoresistance in lung cancer cells. Neutralizing P4HB hampered the tumor growth and increased cisplatin cytotoxic efficacy in two PDX models. Serum P4HB levels were higher in <jats:italic>ARID1A<\/jats:italic>\u2010mutated lung cancer patients than in healthy controls. Moreover, increased serum levels of P4HB were significantly associated with lung cancer metastasis. Together, our work indicates a pivotal role for P4HB in orchestrating the cross\u2010talk between <jats:italic>ARID1A<\/jats:italic>\u2010mutated cancer cells and cancer\u2010associated fibroblasts during lung cancer progression. P4HB may represent a promising target for improving lung cancer treatment.<\/jats:p>","DOI":"10.1111\/cas.16052","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T16:47:35Z","timestamp":1702658855000},"page":"439-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<i>ARID1A<\/i> loss induces <scp>P4HB<\/scp> to activate fibroblasts to support lung cancer cell growth, invasion, and chemoresistance"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4880-847X","authenticated-orcid":false,"given":"Risheng","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery The Dingli Clinical College of Wenzhou Medical University, Wenzhou Central Hospital  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of 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