Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway
Metastasis presents significant challenges in ovarian cancer treatment. Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) facilitate metastasis through epithelial-mesenchymal transition, yet the molecular underlying mechanisms are not fully understood. Here, we identified t...
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2025-02-01
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| author | Yi-Yue Wang Min-Jun Choi Jin-Hyung Kim Jung-Hye Choi |
| author_facet | Yi-Yue Wang Min-Jun Choi Jin-Hyung Kim Jung-Hye Choi |
| author_sort | Yi-Yue Wang |
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| description | Metastasis presents significant challenges in ovarian cancer treatment. Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) facilitate metastasis through epithelial-mesenchymal transition, yet the molecular underlying mechanisms are not fully understood. Here, we identified that tripartite motif-containing 46 (TRIM46) is significantly upregulated in ovarian cancer cells treated with a conditioned medium derived from macrophages stimulated by ovarian cancer cells (OC-MQs). Furthermore, TRIM46 was highly expressed in late-stage ovarian cancer patients and was associated with poor prognosis. Silencing of TRIM46 suppressed cancer cell invasion stimulated by OC-MQ and mesenchymal marker expression without affecting cell viability. Gene set enrichment analysis showed that the Wnt/β-catenin pathway is enriched in the high-TRIM46 expression group. Importantly, the inhibition of TRIM46-mediated β-catenin nuclear translocation and ovarian cancer cell invasion was reversed by CHIR99021, a Wnt/β-catenin activator. Additionally, C-X-C motif chemokine ligand 8 (CXCL8) was identified as being highly expressed in peritoneal MQs from the ascites of ovarian cancer patients and was positively correlated with C-X-C chemokine receptor 1/2 (CXCR1/2) expression in tumor cells. Notably, pre-treatment with reparixin, a CXCR1/2 inhibitor, blocked OC-MQ-induced TRIM46 expression and cell invasion. These results suggest that CXCL8 derived from TAMs promotes human ovarian cancer cell invasion via the Wnt/β-catenin pathway by upregulating TRIM46. |
| format | Article |
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| spelling | doaj-art-fea61cc2605542f4af948bf9f4e541d72025-08-20T02:12:41ZengMDPI AGCells2073-44092025-02-0114321410.3390/cells14030214Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin PathwayYi-Yue Wang0Min-Jun Choi1Jin-Hyung Kim2Jung-Hye Choi3Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, ChinaDepartment of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of KoreaMetastasis presents significant challenges in ovarian cancer treatment. Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) facilitate metastasis through epithelial-mesenchymal transition, yet the molecular underlying mechanisms are not fully understood. Here, we identified that tripartite motif-containing 46 (TRIM46) is significantly upregulated in ovarian cancer cells treated with a conditioned medium derived from macrophages stimulated by ovarian cancer cells (OC-MQs). Furthermore, TRIM46 was highly expressed in late-stage ovarian cancer patients and was associated with poor prognosis. Silencing of TRIM46 suppressed cancer cell invasion stimulated by OC-MQ and mesenchymal marker expression without affecting cell viability. Gene set enrichment analysis showed that the Wnt/β-catenin pathway is enriched in the high-TRIM46 expression group. Importantly, the inhibition of TRIM46-mediated β-catenin nuclear translocation and ovarian cancer cell invasion was reversed by CHIR99021, a Wnt/β-catenin activator. Additionally, C-X-C motif chemokine ligand 8 (CXCL8) was identified as being highly expressed in peritoneal MQs from the ascites of ovarian cancer patients and was positively correlated with C-X-C chemokine receptor 1/2 (CXCR1/2) expression in tumor cells. Notably, pre-treatment with reparixin, a CXCR1/2 inhibitor, blocked OC-MQ-induced TRIM46 expression and cell invasion. These results suggest that CXCL8 derived from TAMs promotes human ovarian cancer cell invasion via the Wnt/β-catenin pathway by upregulating TRIM46.https://www.mdpi.com/2073-4409/14/3/214tumor-associated macrophagesovarian cancerinvasionTRIM46Wnt/β-catenin |
| spellingShingle | Yi-Yue Wang Min-Jun Choi Jin-Hyung Kim Jung-Hye Choi Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway Cells tumor-associated macrophages ovarian cancer invasion TRIM46 Wnt/β-catenin |
| title | Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway |
| title_full | Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway |
| title_fullStr | Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway |
| title_full_unstemmed | Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway |
| title_short | Enhanced Expression of TRIM46 in Ovarian Cancer Cells Induced by Tumor-Associated Macrophages Promotes Invasion via the Wnt/β-Catenin Pathway |
| title_sort | enhanced expression of trim46 in ovarian cancer cells induced by tumor associated macrophages promotes invasion via the wnt β catenin pathway |
| topic | tumor-associated macrophages ovarian cancer invasion TRIM46 Wnt/β-catenin |
| url | https://www.mdpi.com/2073-4409/14/3/214 |
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