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| 標題: | BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation |
| 作者: | Wu, Cheng-Kuei
Wei, Man-Ting
Wu, Hung-Chang
Wu, Cheng-Lin
Wu, Cheng-Ju
Liaw, Hungjiun
Su, Wen-Pin |
| 貢獻者: | National Cheng Kung University
Chi Mei Hospital
Department of Pharmacy, Chia Nan University of Pharmacy & Science
National Cheng Kung University
National Cheng Kung University Hospital
National Cheng Kung University
National Cheng Kung University Hospital
National Cheng Kung University
National Cheng Kung University Hospital
National Cheng Kung University |
| 關鍵字: | bone morphogenetic protein-2
breast-cancer cells
tumor-growth
expression
survival
gene
mutations
melanoma
invasion
tissue |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 14:05:44 (UTC+8) |
| 出版者: | NATURE PORTFOLIO |
| 摘要: | 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. |
| 關聯: | SCIENTIFIC REPORTS, v.12, n.16310 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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