{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:33:47Z","timestamp":1792996427005,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372887"],"award-info":[{"award-number":["82372887"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403045"],"award-info":[{"award-number":["82403045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20240372"],"award-info":[{"award-number":["BK20240372"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent studies have established that the nervous system is not merely a bystander in tumour progression but can actively remodel the tumour microenvironment through the neuro\u2013tumour axis, thereby promoting tumour invasion, metastasis and survival. Semaphorin 3C (SEMA3C) has been reported to regulate tumour migration, angiogenesis and immune suppression, highlighting its potential role in tumour progression. Although the neuro\u2013tumour axis has been identified in multiple cancer types, its role and underlying mechanisms in gastric cancer peritoneal metastasis (GCPM) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single\u2010nucleus RNA sequencing (snRNA\u2010seq) of GCPM tissues to profile tumour cell heterogeneity and identify tumour cell populations associated with neural\u2010related signalling. Candidate tumour\u2013microenvironmental interactions were further investigated using patient\u2010derived organoids and co\u2010culture models, and the identified signalling axis was validated using corresponding in vivo models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SnRNA\u2010seq identified a distinct subpopulation of poorly differentiated tumour cells with pronounced stem\u2010like properties and high SEMA3C expression. This subpopulation was associated with neural\u2010related features and interacted with tumour\u2010associated endothelial cells, thereby contributing to remodelling of the metastatic microenvironment. Furthermore, these cells enhanced tumour\u2013endothelial communication by activating the fibroblast growth factor receptor\u2010associated signalling pathway. The transcription factor early B\u2010cell factor 2 (EBF2) regulates the expression of FGF7 within this subpopulation, thereby strengthening FGF7\u2013FGFR2 signalling and promoting tumour progression. Functional validation further demonstrated that SEMA3C depletion impaired organoid growth and tumour\u2013endothelial interactions, whereas disruption of the SEMA3C\u2013EBF2\u2013FGF7\u2013FGFR2 signalling axis attenuated tumour growth and peritoneal tumour burden in vivo. Additional experimental validation supported the potential involvement of neural\u2010related signalling in the SEMA3C\u2010associated tumour cell state.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings identify a SEMA3C\n                      <jats:sup>+<\/jats:sup>\n                      tumour cell subpopulation associated with neural\u2010related signalling and suggest that SEMA3C promotes tumour\u2013endothelial interactions through the EBF2\u2013FGF7\u2013FGFR2 signalling axis, providing a potential mechanistic link between neural regulation and microenvironmental remodelling in peritoneal metastasis of gastric cancer.\n                    <\/jats:p>\n                  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