BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation
Abstract Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in...
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| Format: | Article |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-20788-2 |
| _version_ | 1811202890964926464 |
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| author | Cheng-Kuei Wu Man-Ting Wei Hung-Chang Wu Cheng-Lin Wu Cheng-Ju Wu Hungjiun Liaw Wen-Pin Su |
| author_facet | Cheng-Kuei Wu Man-Ting Wei Hung-Chang Wu Cheng-Lin Wu Cheng-Ju Wu Hungjiun Liaw Wen-Pin Su |
| author_sort | Cheng-Kuei Wu |
| collection | DOAJ |
| description | Abstract Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 inhibitor significantly reduced cell migration. These findings show that BMP2 promotes NSCLC metastasis, indicating that targeting the BMP2 signaling pathway may represent a potential therapeutic strategy for treating patients with metastatic NSCLC. |
| first_indexed | 2024-04-12T02:45:30Z |
| format | Article |
| id | doaj.art-a606c2360b204f838d35f7a3cf0a21bd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T02:45:30Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a606c2360b204f838d35f7a3cf0a21bd2022-12-22T03:51:11ZengNature PortfolioScientific Reports2045-23222022-09-0112111310.1038/s41598-022-20788-2BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activationCheng-Kuei Wu0Man-Ting Wei1Hung-Chang Wu2Cheng-Lin Wu3Cheng-Ju Wu4Hungjiun Liaw5Wen-Pin Su6Institute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDivision of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical CenterInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartments of Oncology and Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Life Sciences, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityAbstract Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 inhibitor significantly reduced cell migration. These findings show that BMP2 promotes NSCLC metastasis, indicating that targeting the BMP2 signaling pathway may represent a potential therapeutic strategy for treating patients with metastatic NSCLC.https://doi.org/10.1038/s41598-022-20788-2 |
| spellingShingle | Cheng-Kuei Wu Man-Ting Wei Hung-Chang Wu Cheng-Lin Wu Cheng-Ju Wu Hungjiun Liaw Wen-Pin Su BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation Scientific Reports |
| title | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| title_full | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| title_fullStr | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| title_full_unstemmed | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| title_short | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| title_sort | bmp2 promotes lung adenocarcinoma metastasis through bmp receptor 2 mediated smad1 5 activation |
| url | https://doi.org/10.1038/s41598-022-20788-2 |
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