BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation

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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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