Reference - Detail
| RRC ID | 85034 |
|---|---|
| Author | Kanoda R, Nakajima S, Okayama H, Kaneta A, Chida S, Matsumoto T, Saito K, Kikuchi T, Maruyama Y, Suzuki H, Mimura K, Saito M, Hanayama H, Sakamoto W, Momma T, Saze Z, Kono K. |
| Title | Downregulation of cGAS/STING expression in tumor cells by cancer-associated fibroblasts in colorectal cancer. |
| Journal | Sci Rep |
| Abstract |
The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for activating anti-tumor immunity and enhancing immune checkpoint blockade therapy in colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs), key components of the CRC tumor microenvironment, negatively regulate the anti-tumor immune response. However, their impact on tumor cell-intrinsic cGAS-STING expression remains unclear. In the present study, we investigated whether CAFs can downregulate cGAS-STING expression in CRC. We found that cGAS-STING expression in tumor cells inversely correlated with stromal expression of versican (VCAN), an immunosuppressive CAF marker, in CRC tissues. Co-culture experiments using primary human CAFs derived from CRC tissues revealed that CAFs downregulated cGAS and/or STING expression in CRC cell lines (WiDr, LoVo, HCT116). Furthermore, CAFs expressing VCAN and fibronectin 1 appeared to mediate this suppression. These findings suggest that immunosuppressive CAFs contribute to the downregulation of tumor cell-intrinsic cGAS-STING expression in CRC. Therefore, targeting CAFs to restore cGAS-STING expression may represent a promising strategy to enhance the efficacy of CRC treatment. |
| Volume | 15(1) |
| Pages | 19234 |
| Published | 2025-6-2 |
| DOI | 10.1038/s41598-025-03924-6 |
| PII | 10.1038/s41598-025-03924-6 |
| PMID | 40451897 |
| PMC | PMC12127464 |
| MeSH | Cancer-Associated Fibroblasts* / metabolism Cancer-Associated Fibroblasts* / pathology Cell Line, Tumor Coculture Techniques Colorectal Neoplasms* / genetics Colorectal Neoplasms* / metabolism Colorectal Neoplasms* / pathology Down-Regulation Female Fibronectins / metabolism Gene Expression Regulation, Neoplastic HCT116 Cells Humans Male Membrane Proteins* / genetics Membrane Proteins* / metabolism Nucleotidyltransferases* / genetics Nucleotidyltransferases* / metabolism Tumor Microenvironment Versicans / genetics Versicans / metabolism |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HCT116(RCB2979) |