The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma
Abstract Background Profilin 2 (PFN2), indispensable in all organisms, is important for cancer initiation and progression. Here, we found PFN2 highly overexpressed in tumor tissues with poor prognosis of Lung adenocarcinoma (LUAD) patients had a novel role in remodulating angiogenesis. However, the...
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BMC
2025-05-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03281-y |
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| author | Xiaohui Du Chi Ma Yingyan Wang Mingxin Xu Yanbin Kuang Mengyun Li Shuang Wen Peipei He Hui Zhao Qi Wang |
| author_facet | Xiaohui Du Chi Ma Yingyan Wang Mingxin Xu Yanbin Kuang Mengyun Li Shuang Wen Peipei He Hui Zhao Qi Wang |
| author_sort | Xiaohui Du |
| collection | DOAJ |
| description | Abstract Background Profilin 2 (PFN2), indispensable in all organisms, is important for cancer initiation and progression. Here, we found PFN2 highly overexpressed in tumor tissues with poor prognosis of Lung adenocarcinoma (LUAD) patients had a novel role in remodulating angiogenesis. However, the mechanism of PFN2-mediated LUAD angiogenesis remains unelucided. Methods Immunohistochemistry and western blotting were used to detected the expression levels of related proteins in tissue or lung cancer cells. To elucidate the underlying mechanisms, we identified binding partners of PFN2 through mass spectrometry, co-immunoprecipitation, and molecular modeling techniques. Additionally, we investigated the angiogenic-promoting function of PFN2 utilizing a three-dimensional droplet-based angiogenesis model capable of simulating the tumor hypoxic microenvironment. Results Our finding reveal that PFN2 was overexpressed in tumors compared with the adjacent nontumor tissues. Its knockdown markedly impaired the proliferation, and angiogenesis of LUAD cells via hypoxia-related NF-κB/HIF-1α signaling pathway, with vascular endothelial growth Factor (VEGF) decrease. Additionally, pyruvate kinase M2 (PKM2), a pivotal enzyme in glycolysis, is a novel binding partner of PFN2. The nuclear translocation of PKM2 was observed to be dependent on PFN2 expression and their interaction, which functionally modulates angiogenesis in lung cancer. Conclusions Our study revealed oncogene PFN2 promoted tumor angiogenesis in LUAD through regulating PKM2 nuclear translocation, providing novel molecular therapy targets for LUAD treatment. |
| format | Article |
| id | doaj-art-259ab823c73145fbb98db3170f51c3ae |
| institution | DOAJ |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-259ab823c73145fbb98db3170f51c3ae2025-08-20T03:16:41ZengBMCRespiratory Research1465-993X2025-05-0126111510.1186/s12931-025-03281-yThe novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinomaXiaohui Du0Chi Ma1Yingyan Wang2Mingxin Xu3Yanbin Kuang4Mengyun Li5Shuang Wen6Peipei He7Hui Zhao8Qi Wang9Department of Scientific Research Center, the Second Affiliated Hospital, Dalian Medical UniversityDepartment of Respiratory Medicine, the Second Affiliated Hospital, Dalian Medical UniversityLaboratory Center for Diagnostics, Dalian Medical UniversityDepartment of Respiratory Medicine, the Second Affiliated Hospital, Dalian Medical UniversityDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityDepartment of Respiratory Medicine, the Second Affiliated Hospital, Dalian Medical UniversityDepartment of Pathology, Dalian Friendship HospitalDepartment of Respiratory Medicine, the Second Affiliated Hospital, Dalian Medical UniversityDepartment of Health Examination Center, the Second Affiliated Hospital, Dalian Medical UniversityDepartment of Respiratory Medicine, the Second Affiliated Hospital, Dalian Medical UniversityAbstract Background Profilin 2 (PFN2), indispensable in all organisms, is important for cancer initiation and progression. Here, we found PFN2 highly overexpressed in tumor tissues with poor prognosis of Lung adenocarcinoma (LUAD) patients had a novel role in remodulating angiogenesis. However, the mechanism of PFN2-mediated LUAD angiogenesis remains unelucided. Methods Immunohistochemistry and western blotting were used to detected the expression levels of related proteins in tissue or lung cancer cells. To elucidate the underlying mechanisms, we identified binding partners of PFN2 through mass spectrometry, co-immunoprecipitation, and molecular modeling techniques. Additionally, we investigated the angiogenic-promoting function of PFN2 utilizing a three-dimensional droplet-based angiogenesis model capable of simulating the tumor hypoxic microenvironment. Results Our finding reveal that PFN2 was overexpressed in tumors compared with the adjacent nontumor tissues. Its knockdown markedly impaired the proliferation, and angiogenesis of LUAD cells via hypoxia-related NF-κB/HIF-1α signaling pathway, with vascular endothelial growth Factor (VEGF) decrease. Additionally, pyruvate kinase M2 (PKM2), a pivotal enzyme in glycolysis, is a novel binding partner of PFN2. The nuclear translocation of PKM2 was observed to be dependent on PFN2 expression and their interaction, which functionally modulates angiogenesis in lung cancer. Conclusions Our study revealed oncogene PFN2 promoted tumor angiogenesis in LUAD through regulating PKM2 nuclear translocation, providing novel molecular therapy targets for LUAD treatment.https://doi.org/10.1186/s12931-025-03281-yProfilin 2Pyruvate kinase M2Lung adenocarcinomaAngiogenesis |
| spellingShingle | Xiaohui Du Chi Ma Yingyan Wang Mingxin Xu Yanbin Kuang Mengyun Li Shuang Wen Peipei He Hui Zhao Qi Wang The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma Respiratory Research Profilin 2 Pyruvate kinase M2 Lung adenocarcinoma Angiogenesis |
| title | The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| title_full | The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| title_fullStr | The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| title_full_unstemmed | The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| title_short | The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| title_sort | novelty of profilin 2 in regulating pyruvate kinase m2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma |
| topic | Profilin 2 Pyruvate kinase M2 Lung adenocarcinoma Angiogenesis |
| url | https://doi.org/10.1186/s12931-025-03281-y |
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