SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway
<b>Background:</b> Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. <b>Methods&...
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2025-04-01
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| author | Ranran Chai Kewei Zheng Ting Xu Hui Wang Xiaobo Cheng Chong Lu Yu Kang |
| author_facet | Ranran Chai Kewei Zheng Ting Xu Hui Wang Xiaobo Cheng Chong Lu Yu Kang |
| author_sort | Ranran Chai |
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| description | <b>Background:</b> Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. <b>Methods</b>: The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed using single-cell datasets (GSE147082, GSE58937). The Kaplan–Meier Plotter and GEPIA2 databases were used to evaluate SNX10’s prognostic relevance. Lentivirus-mediated <i>SNX10</i> overexpression in THP-1 cells was employed in tumor cell–macrophage co-culture experiments. Transwell assays and flow cytometry assessed SNX10’s effects on ovarian cancer cell metastasis and cisplatin-induced apoptosis. RNA sequencing, Western blotting, lysosomal pH detection, lipid droplet staining, and RT-qPCR were performed to explore SNX10’s molecular mechanisms in TAM polarization and immune modulation. <b>Results</b>: SNX10 was specifically expressed in TAMs, promoting their polarization into the M2 phenotype. This enhanced the migration and invasion of ovarian cancer cell lines A2780 and A2780/CP70 while reducing cisplatin-induced apoptosis. SNX10 decreased lipid droplet content, downregulated p-mTOR1, and impaired lysosomal function in TAMs. Additionally, SNX10 differentially modulated <i>PD-L1</i> mRNA expression in platinum-sensitive and platinum-resistant ovarian cancer cells. <b>Conclusions</b>: SNX10 regulates the mTOR1/lysosome pathway in TAMs, influencing lipid metabolism and indirectly modulating ovarian cancer cell metastasis. It also alters <i>PD-L1</i> mRNA expression, suggesting a role in shaping the tumor immune microenvironment. |
| format | Article |
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| spelling | doaj-art-e9bdbfe964b649a88b6108550e674fc92025-08-20T01:56:29ZengMDPI AGBiomedicines2227-90592025-04-01135102110.3390/biomedicines13051021SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes PathwayRanran Chai0Kewei Zheng1Ting Xu2Hui Wang3Xiaobo Cheng4Chong Lu5Yu Kang6Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China<b>Background:</b> Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. <b>Methods</b>: The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed using single-cell datasets (GSE147082, GSE58937). The Kaplan–Meier Plotter and GEPIA2 databases were used to evaluate SNX10’s prognostic relevance. Lentivirus-mediated <i>SNX10</i> overexpression in THP-1 cells was employed in tumor cell–macrophage co-culture experiments. Transwell assays and flow cytometry assessed SNX10’s effects on ovarian cancer cell metastasis and cisplatin-induced apoptosis. RNA sequencing, Western blotting, lysosomal pH detection, lipid droplet staining, and RT-qPCR were performed to explore SNX10’s molecular mechanisms in TAM polarization and immune modulation. <b>Results</b>: SNX10 was specifically expressed in TAMs, promoting their polarization into the M2 phenotype. This enhanced the migration and invasion of ovarian cancer cell lines A2780 and A2780/CP70 while reducing cisplatin-induced apoptosis. SNX10 decreased lipid droplet content, downregulated p-mTOR1, and impaired lysosomal function in TAMs. Additionally, SNX10 differentially modulated <i>PD-L1</i> mRNA expression in platinum-sensitive and platinum-resistant ovarian cancer cells. <b>Conclusions</b>: SNX10 regulates the mTOR1/lysosome pathway in TAMs, influencing lipid metabolism and indirectly modulating ovarian cancer cell metastasis. It also alters <i>PD-L1</i> mRNA expression, suggesting a role in shaping the tumor immune microenvironment.https://www.mdpi.com/2227-9059/13/5/1021ovarian cancertumor associated macrophagesSNX10lysosomemTOR1 |
| spellingShingle | Ranran Chai Kewei Zheng Ting Xu Hui Wang Xiaobo Cheng Chong Lu Yu Kang SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway Biomedicines ovarian cancer tumor associated macrophages SNX10 lysosome mTOR1 |
| title | SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway |
| title_full | SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway |
| title_fullStr | SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway |
| title_full_unstemmed | SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway |
| title_short | SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway |
| title_sort | snx10 is involved in ovarian cancer cell metastasis by repolarizing tumor associated macrophages through mtor1 lysosomes pathway |
| topic | ovarian cancer tumor associated macrophages SNX10 lysosome mTOR1 |
| url | https://www.mdpi.com/2227-9059/13/5/1021 |
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