{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:54:04Z","timestamp":1792788844137,"version":"4.5.0"},"reference-count":23,"publisher":"Bioscientifica","issue":"10","funder":[{"name":"National Natural Science Foundation of China","award":["81771865"],"award-info":[{"award-number":["81771865"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) in papillary thyroid carcinoma (PTC) and play a critical role in disease progression. We previously reported that interleukin-6 (IL-6) promotes PTC progression through activation of MAPK signaling. However, whether CAFs serve as a major source of IL-6 and the underlying regulatory mechanisms remain incompletely understood. By integrating single-cell RNA-seq data from patients with PTC, we identified fibroblasts as the predominant cellular source of IL-6, with IL-6 expression positively correlated with the CAF marker ACTA2. Primary CAFs isolated from PTC tissues exhibited enhanced proliferation, migration, glycolysis, and IL-6 secretion compared with normal fibroblasts (NFs), and these phenotypes were further potentiated by hypoxia. Mechanistically, hypoxia-induced reactive oxygen species (ROS) accumulation in CAFs, which activated NF-\u03baB signaling to drive IL-6 production. Blocking NF-\u03baB with JSH-23 or scavenging ROS with NAC or MitoQ abrogated hypoxia-induced IL-6 expression. In non-contact co-cultures, CAF-derived IL-6 promoted PTC cell proliferation and MAPK pathway activation under hypoxia, whereas IL-6 knockdown reversed these effects. In vivo, co-injection of CAFs with PTC cells enhanced tumor growth, which was significantly suppressed by the IL-6 receptor blocker tocilizumab. Collectively, these findings reveal that hypoxia activates a ROS\/NF-\u03baB\/IL-6 axis in CAFs, which in turn drives PTC progression through paracrine IL-6 signaling. Targeting this pathway may represent a potential therapeutic strategy for aggressive PTC.<\/jats:p>","DOI":"10.1530\/erc-26-0198","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:17:01Z","timestamp":1791451021000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Cancer-associated fibroblasts drive papillary thyroid cancer progression through ROS\/NF-\u03baB\/IL-6 signaling in hypoxic microenvironments"],"prefix":"10.1530","volume":"33","author":[{"given":"Hongjun","family":"Song","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 1 , ,","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhao","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Thyroid, Parathyroid, Breast and Hernia 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