دورية أكاديمية
YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling
العنوان: | YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling |
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المؤلفون: | Hua Sui, Wanli Deng, Qiong Chai, Bing Han, Yuli Zhang, Zhenzhen Wei, Zan Li, Ting Wang, Jiling Feng, Man Yuan, Qingfeng Tang, Hongxi Xu |
المصدر: | Journal of Pharmaceutical Analysis, Vol 14, Iss 4, Pp 100901- (2024) |
بيانات النشر: | Elsevier, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Therapeutics. Pharmacology |
مصطلحات موضوعية: | Tumor microenvironment, Intestinal epithelial cells, Treg/Th17 cells, Metabolism, Wnt5a/JNK signaling, Tumorigenesis, Therapeutics. Pharmacology, RM1-950 |
الوصف: | The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and in vivo, revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2095-1779 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2095177923002745; https://doaj.org/toc/2095-1779 |
DOI: | 10.1016/j.jpha.2023.11.008 |
URL الوصول: | https://doaj.org/article/10aa83ee386f4478848b4541aefe3596 |
رقم الأكسشن: | edsdoj.10aa83ee386f4478848b4541aefe3596 |
قاعدة البيانات: | Directory of Open Access Journals |
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