CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20
Background 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...
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Taylor & Francis Group
2025-12-01
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| Series: | Autoimmunity |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/08916934.2025.2458324 |
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| author | Chen Zheng Hu Hei Yifei Zhai Wenbo Gong Runfang Zhang Songtao Zhang |
| author_facet | Chen Zheng Hu Hei Yifei Zhai Wenbo Gong Runfang Zhang Songtao Zhang |
| author_sort | Chen Zheng |
| collection | DOAJ |
| description | Background 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.Methods The mRNA and protein levels were examined via 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. In vivo assays were performed by establishing xenograft models.Results CREB1 was highly expressed in TC. CREB1 positively interacted with CCL20 in TC. CREB1 facilitated TC cell migration, invasion and proliferation via 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.Conclusion CAFs-derived exosomes accelerated the malignant behaviors and immune evasion in TC by carrying CREB1 to up-regulate CCL20. |
| format | Article |
| id | doaj-art-baffd1968c9e4da0aac58b4f1b1395be |
| institution | Kabale University |
| issn | 0891-6934 1607-842X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj-art-baffd1968c9e4da0aac58b4f1b1395be2025-01-26T04:09:22ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2025-12-0158110.1080/08916934.2025.2458324CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20Chen Zheng0Hu Hei1Yifei Zhai2Wenbo Gong3Runfang Zhang4Songtao Zhang5Department of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, ChinaBackground 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.Methods The mRNA and protein levels were examined via 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. In vivo assays were performed by establishing xenograft models.Results CREB1 was highly expressed in TC. CREB1 positively interacted with CCL20 in TC. CREB1 facilitated TC cell migration, invasion and proliferation via 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.Conclusion CAFs-derived exosomes accelerated the malignant behaviors and immune evasion in TC by carrying CREB1 to up-regulate CCL20.https://www.tandfonline.com/doi/10.1080/08916934.2025.2458324CREB1CCL20CAFs-derived exosomesthyroid cancerimmune evasion |
| spellingShingle | Chen Zheng Hu Hei Yifei Zhai Wenbo Gong Runfang Zhang Songtao Zhang CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 Autoimmunity CREB1 CCL20 CAFs-derived exosomes thyroid cancer immune evasion |
| title | CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 |
| title_full | CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 |
| title_fullStr | CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 |
| title_full_unstemmed | CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 |
| title_short | CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20 |
| title_sort | cafs released exosomal creb1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of ccl20 |
| topic | CREB1 CCL20 CAFs-derived exosomes thyroid cancer immune evasion |
| url | https://www.tandfonline.com/doi/10.1080/08916934.2025.2458324 |
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