Zheng Chen, Hei Hu, Zhai Yifei, Gong Wenbo, Zhang Runfang, Zhang Songtao
Department of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Autoimmunity. 2025 Dec;58(1):2458324. doi: 10.1080/08916934.2025.2458324. Epub 2025 Jan 25.
Exosomes derived from cancer-associated fibroblasts (CAFs) can affect tumor microenvironment (TME) of thyroid cancer (TC). The cAMP response element binding protein 1 (CREB1) acts as a transcription factor to participate in cancer development. Currently, we aimed to explore the molecular mechanism of exosome-associated CREB1 and C-C motif chemokine ligand 20 (CCL20) in TC.
The mRNA and protein levels were examined RT-qPCR and western blot. Gene interaction was analyzed using ChIP and dual-luciferase reporter assays. Cell migration, invasion and proliferation were assessed by wound healing, transwell and EdU assays. Exosomes were characterized by morphology observation and western blot. The proliferation and apoptosis of CD8 T cells were detected by immunofluorescence and flow cytometry. assays were performed by establishing xenograft models.
CREB1 was highly expressed in TC. CREB1 positively interacted with CCL20 in TC. CREB1 facilitated TC cell migration, invasion and proliferation targeting CCL20. CCL20 expression was reduced by transferring CAFs-secreted exosomes sheltering CREB1 downregulation. Exosomal CREB1 knockdown receded cell progression and enhanced CD8 T function by mediating CCL20. CAFs-associated exosomal CREB1 downregulation inhibited tumorigenesis through affecting CCL20.
CAFs-derived exosomes accelerated the malignant behaviors and immune evasion in TC by carrying CREB1 to up-regulate CCL20.
源自癌症相关成纤维细胞（CAFs）的外泌体可影响甲状腺癌（TC）的肿瘤微环境（TME）。环磷酸腺苷反应元件结合蛋白1（CREB1）作为一种转录因子参与癌症发展。目前，我们旨在探索外泌体相关的CREB1和C-C基序趋化因子配体20（CCL20）在甲状腺癌中的分子机制。
采用RT-qPCR和蛋白质印迹法检测mRNA和蛋白质水平。使用染色质免疫沉淀（ChIP）和双荧光素酶报告基因测定法分析基因相互作用。通过伤口愈合、Transwell和EdU测定法评估细胞迁移、侵袭和增殖。通过形态学观察和蛋白质印迹对外泌体进行表征。通过免疫荧光和流式细胞术检测CD8 T细胞的增殖和凋亡。通过建立异种移植模型进行实验。
CREB1在甲状腺癌中高表达。CREB1与甲状腺癌中的CCL20呈正相互作用。CREB1通过靶向CCL20促进甲状腺癌细胞的迁移、侵袭和增殖。通过转染携带CREB1下调的CAFs分泌的外泌体，CCL20表达降低。外泌体CREB1敲低通过介导CCL20减弱细胞进展并增强CD8 T细胞功能。CAFs相关的外泌体CREB1下调通过影响CCL20抑制肿瘤发生。
CAFs来源的外泌体通过携带CREB1上调CCL20，加速甲状腺癌的恶性行为和免疫逃逸。
