{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:37:25Z","timestamp":1793756245462,"version":"4.6.1"},"reference-count":68,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272990"],"award-info":[{"award-number":["82272990"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Gastric cancer (GC) is one of the most common tumours in East Asia countries and is associated with\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      infection.\n                      <jats:italic>H. pylori<\/jats:italic>\n                      utilizes virulence factors, CagA and VacA, to up\u2010regulate pro\u2010inflammatory cytokines and activate NF\u2010\u03baB signaling. Meanwhile, the PIEZO1 upregulation and cancer\u2010associated fibroblast (CAF) enrichment were found in GC progression. However, the mechanisms of PIEZO1 upregulation and its involvement in GC progression have not been fully elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The CAF enrichment and clinical significance were investigated in animal models and primary samples. The expression of NF\u2010\u03baB and PIEZO1 in GC was confirmed by immunohistochemistry staining, and expression correlation was analysed in multiple GC datasets. GSEA and Western blot analysis revealed the YAP1\u2010CTGF axis regulation by PIEZO1. The stimulatory effects of CTGF on CAFs were validated by the co\u2010culture system and animal studies. Patient\u2010derived organoid and peritoneal dissemination models were employed to confirm the role of the PIEZO1\u2010YAP1\u2010CTGF cascade in GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both CAF signature and PIEZO1 were positively correlated with\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection. PIEZO1, a mechanosensor, was confirmed as a direct downstream of NF\u2010\u03baB to promote the transformation from intestinal metaplasia to GC. Mechanistic studies revealed that PIEZO1 transduced the oncogenic signal from NF\u2010\u03baB into YAP1 signaling, a well\u2010documented oncogenic pathway in GC progression. PIEZO1 expression was positively correlated with the YAP1 signature (CTGF, CYR61, and c\u2010Myc, etc.) in primary samples. The secreted CTGF by cancer cells stimulated the CAF infiltration to form a stiffened collagen\u2010enrichment microenvironment, thus activating PIEZO1 to form a positive feedback loop. Both PIEZO1 depletion by shRNA and CTGF inhibition by Procyanidin C1 enhanced the efficacy of 5\u2010FU in suppressing the GC cell peritoneal metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study elucidates a novel driving PIEZO1\u2010YAP1\u2010CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC.\n                      <jats:italic>H. pylori<\/jats:italic>\n                      \u2010NF\u2010\u03baB activates the PIEZO1\u2010YAP1\u2010CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1\u2010YAP1\u2010CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1481","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T16:49:27Z","timestamp":1700585367000},"source":"Crossref","is-referenced-by-count":93,"title":["<i>H. pylori<\/i>\n                    \u2010induced NF\u2010\u03baB\u2010PIEZO1\u2010YAP1\u2010CTGF axis drives gastric cancer progression and cancer\u2010associated fibroblast\u2010mediated tumour microenvironment remodelling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2430-7934","authenticated-orcid":false,"given":"Bonan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anatomical and Cellular Pathology State Key Laboratory of Translational Oncology Sir Y.K. 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Pao Cancer Center Prince of Wales Hospital The Chinese University of Hong Kong  Hong Kong China"},{"name":"Institute of Digestive Disease State Key Laboratory of Digestive Disease Li Ka Shing Institute of Health Science The Chinese University of Hong Kong  Hong Kong China"},{"name":"CUHK\u2010Shenzhen Research Institute  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuda","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology State Key Laboratory of Translational Oncology Sir Y.K. 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