C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma
Abstract Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers in Southern China and Southeast Asia. Although current studies have adequately characterized the tumor microenvironment (TME) of NPC, little attention has been paid to how cell‐cell interactions within the TME promote...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202503434 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849239393148076032 |
|---|---|
| author | Yunzhi Liu Cuicui Huang Min Luo Wenfu Lu Baifeng Zhang Lu Bai Shuyue Zheng Yanan Tan Shanshan Li Huali Wang Lanqi Gong Xinyuan Guan |
| author_facet | Yunzhi Liu Cuicui Huang Min Luo Wenfu Lu Baifeng Zhang Lu Bai Shuyue Zheng Yanan Tan Shanshan Li Huali Wang Lanqi Gong Xinyuan Guan |
| author_sort | Yunzhi Liu |
| collection | DOAJ |
| description | Abstract Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers in Southern China and Southeast Asia. Although current studies have adequately characterized the tumor microenvironment (TME) of NPC, little attention has been paid to how cell‐cell interactions within the TME promote tumorigenesis. In this study, it is found that C1q+ tumor‐associated macrophages (TAMs) are significantly enriched in NPC tumors. Moreover, both enriched C1q+ TAMs and elevated C1q expression are associated with the progression and poor prognosis in NPC patients. In vitro and in vivo studies demonstrate that C1q directly boosts the malignancy and stemness of tumor cells. Mechanistically, C1q activates the Phosphatidylinositol‐3‐kinase (PI3K)/AKT pathway through interacting with GPR17, a member of the G protein‐coupled receptor family, thereby inducing DNA hypermethylation of tumor cells to promote tumor development. It is further proved that DNA hypermethylated NPC cells induced by C1q elicited the immunosuppressive phenotype of TAMs. Targeted blockade of C1q with a neutralizing antibody restricts NPC progression in the humanized mouse model. It is assumed that the differentiation of C1q+ TAMs possibly acquired both M1 and M2 polarization conditions. These findings provide new insights into the cellular communication in the TME of NPC and may have important applications for the development of new targeted therapies. |
| format | Article |
| id | doaj-art-a1b1ee406e88405a981024c1796ecbf2 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a1b1ee406e88405a981024c1796ecbf22025-08-20T04:01:01ZengWileyAdvanced Science2198-38442025-07-011226n/an/a10.1002/advs.202503434C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal CarcinomaYunzhi Liu0Cuicui Huang1Min Luo2Wenfu Lu3Baifeng Zhang4Lu Bai5Shuyue Zheng6Yanan Tan7Shanshan Li8Huali Wang9Lanqi Gong10Xinyuan Guan11Clinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaDepartment of Surgery Division of Otolaryngology, Head and Neck Surgery The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaClinical Oncology Center Shenzhen Key Laboratory for cancer metastasis and personalized therapy The University of Hong Kong‐Shenzhen Hospital Shenzhen 518053 ChinaAbstract Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers in Southern China and Southeast Asia. Although current studies have adequately characterized the tumor microenvironment (TME) of NPC, little attention has been paid to how cell‐cell interactions within the TME promote tumorigenesis. In this study, it is found that C1q+ tumor‐associated macrophages (TAMs) are significantly enriched in NPC tumors. Moreover, both enriched C1q+ TAMs and elevated C1q expression are associated with the progression and poor prognosis in NPC patients. In vitro and in vivo studies demonstrate that C1q directly boosts the malignancy and stemness of tumor cells. Mechanistically, C1q activates the Phosphatidylinositol‐3‐kinase (PI3K)/AKT pathway through interacting with GPR17, a member of the G protein‐coupled receptor family, thereby inducing DNA hypermethylation of tumor cells to promote tumor development. It is further proved that DNA hypermethylated NPC cells induced by C1q elicited the immunosuppressive phenotype of TAMs. Targeted blockade of C1q with a neutralizing antibody restricts NPC progression in the humanized mouse model. It is assumed that the differentiation of C1q+ TAMs possibly acquired both M1 and M2 polarization conditions. These findings provide new insights into the cellular communication in the TME of NPC and may have important applications for the development of new targeted therapies.https://doi.org/10.1002/advs.202503434C1qDNA hypermethylationnasopharyngeal carcinomaPI3K/AKT signalingtumor‐associated macrophage |
| spellingShingle | Yunzhi Liu Cuicui Huang Min Luo Wenfu Lu Baifeng Zhang Lu Bai Shuyue Zheng Yanan Tan Shanshan Li Huali Wang Lanqi Gong Xinyuan Guan C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma Advanced Science C1q DNA hypermethylation nasopharyngeal carcinoma PI3K/AKT signaling tumor‐associated macrophage |
| title | C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma |
| title_full | C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma |
| title_fullStr | C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma |
| title_full_unstemmed | C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma |
| title_short | C1q+ Macrophage–Tumor Cell Interaction Promoted Tumorigenesis via GPR17/PI3K/AKT Pathway Induced DNA Hypermethylation in Nasopharyngeal Carcinoma |
| title_sort | c1q macrophage tumor cell interaction promoted tumorigenesis via gpr17 pi3k akt pathway induced dna hypermethylation in nasopharyngeal carcinoma |
| topic | C1q DNA hypermethylation nasopharyngeal carcinoma PI3K/AKT signaling tumor‐associated macrophage |
| url | https://doi.org/10.1002/advs.202503434 |
| work_keys_str_mv | AT yunzhiliu c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT cuicuihuang c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT minluo c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT wenfulu c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT baifengzhang c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT lubai c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT shuyuezheng c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT yanantan c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT shanshanli c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT hualiwang c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT lanqigong c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma AT xinyuanguan c1qmacrophagetumorcellinteractionpromotedtumorigenesisviagpr17pi3kaktpathwayinduceddnahypermethylationinnasopharyngealcarcinoma |