PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling
Bone metastases frequently occur in NSCLC patients at the late stage, indicating poor survival. However, mechanisms about the initiation of NSCLC bone metastases remain largely unclear. In our previous reports, BMP2 signaling activation has been found to enhance NSCLC bone metastases through enhanci...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.678931/full |
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| author | Fei Huang Fei Huang Fei Huang Yaqiang Cao Caihong Wang Caihong Wang Ruilong Lan Ruilong Lan Ruilong Lan Bing Wu Bing Wu Bing Wu Xianhe Xie Jinsheng Hong Jinsheng Hong Lengxi Fu Lengxi Fu Lengxi Fu Gui Wu |
| author_facet | Fei Huang Fei Huang Fei Huang Yaqiang Cao Caihong Wang Caihong Wang Ruilong Lan Ruilong Lan Ruilong Lan Bing Wu Bing Wu Bing Wu Xianhe Xie Jinsheng Hong Jinsheng Hong Lengxi Fu Lengxi Fu Lengxi Fu Gui Wu |
| author_sort | Fei Huang |
| collection | DOAJ |
| description | Bone metastases frequently occur in NSCLC patients at the late stage, indicating poor survival. However, mechanisms about the initiation of NSCLC bone metastases remain largely unclear. In our previous reports, BMP2 signaling activation has been found to enhance NSCLC bone metastases through enhancing carcinoma cells migration, invasion, osteoclasts differentiation and osteoblasts immature differentiation. Nevertheless, downstream target genes of BMP2 contributing to those processes still remain unknown. In this project, we find that the expression of Pnma5 is higher in metastatic bone tumors of Lewis lung carcinoma than in metastatic lung tumors and parental Lewis lung cells. Pnma5 overexpression not only can promote cell migration and invasion of NSCLC cells but also tumor-induced osteoclasts differentiation. Interestingly, knockdown of Pnma5 in Lewis lung cells blocks BMP2 signaling from inducing Lewis lung cells migration and invasion. Although BMP2 signaling can promote Lewis lung cells-induced osteoclasts differentiation from macrophages, this effect can also be blocked when Pnma5 is knocked down in Lewis lung cells. Moreover, Pnma5 can promote NSCLC bone metastases in vivo as the downstream target of BMP2. Those results above indicate that BMP2 signaling enhances NSCLC bone metastases via its direct downstream target gene Pnma5. This research reveals the detailed molecular mechanism about how BMP2 signaling contributes to NSCLC bone metastases via PNMA5 and provides a new potential therapeutic target for the treatment of NSCLC bone metastases. |
| first_indexed | 2024-12-17T07:13:59Z |
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| language | English |
| last_indexed | 2024-12-17T07:13:59Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-57d59d178e65473291101ded8dcb1d542022-12-21T21:58:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-05-01910.3389/fcell.2021.678931678931PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 SignalingFei Huang0Fei Huang1Fei Huang2Yaqiang Cao3Caihong Wang4Caihong Wang5Ruilong Lan6Ruilong Lan7Ruilong Lan8Bing Wu9Bing Wu10Bing Wu11Xianhe Xie12Jinsheng Hong13Jinsheng Hong14Lengxi Fu15Lengxi Fu16Lengxi Fu17Gui Wu18Central Lab, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Radiation Oncology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaCentral Lab, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaCentral Lab, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Chemotherapy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Radiation Oncology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaCentral Lab, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaBone metastases frequently occur in NSCLC patients at the late stage, indicating poor survival. However, mechanisms about the initiation of NSCLC bone metastases remain largely unclear. In our previous reports, BMP2 signaling activation has been found to enhance NSCLC bone metastases through enhancing carcinoma cells migration, invasion, osteoclasts differentiation and osteoblasts immature differentiation. Nevertheless, downstream target genes of BMP2 contributing to those processes still remain unknown. In this project, we find that the expression of Pnma5 is higher in metastatic bone tumors of Lewis lung carcinoma than in metastatic lung tumors and parental Lewis lung cells. Pnma5 overexpression not only can promote cell migration and invasion of NSCLC cells but also tumor-induced osteoclasts differentiation. Interestingly, knockdown of Pnma5 in Lewis lung cells blocks BMP2 signaling from inducing Lewis lung cells migration and invasion. Although BMP2 signaling can promote Lewis lung cells-induced osteoclasts differentiation from macrophages, this effect can also be blocked when Pnma5 is knocked down in Lewis lung cells. Moreover, Pnma5 can promote NSCLC bone metastases in vivo as the downstream target of BMP2. Those results above indicate that BMP2 signaling enhances NSCLC bone metastases via its direct downstream target gene Pnma5. This research reveals the detailed molecular mechanism about how BMP2 signaling contributes to NSCLC bone metastases via PNMA5 and provides a new potential therapeutic target for the treatment of NSCLC bone metastases.https://www.frontiersin.org/articles/10.3389/fcell.2021.678931/fullPNMA5NSCLCbone metastasesBMP2target gene |
| spellingShingle | Fei Huang Fei Huang Fei Huang Yaqiang Cao Caihong Wang Caihong Wang Ruilong Lan Ruilong Lan Ruilong Lan Bing Wu Bing Wu Bing Wu Xianhe Xie Jinsheng Hong Jinsheng Hong Lengxi Fu Lengxi Fu Lengxi Fu Gui Wu PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling Frontiers in Cell and Developmental Biology PNMA5 NSCLC bone metastases BMP2 target gene |
| title | PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling |
| title_full | PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling |
| title_fullStr | PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling |
| title_full_unstemmed | PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling |
| title_short | PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling |
| title_sort | pnma5 promotes bone metastasis of non small cell lung cancer as a target of bmp2 signaling |
| topic | PNMA5 NSCLC bone metastases BMP2 target gene |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.678931/full |
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