BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway

• Published in: Aging (Albany, NY.) Vol. 9; no. 4; pp. 1326 - 1340
• Main Authors: Wang, Meng-He, Zhou, Xiao-Min, Zhang, Mei-Yin, Shi, Lu, Xiao, Ruo-Wen, Zeng, Li-Si, Yang, Xian-Zi, Zheng, X F Steven, Wang, Hui-Yun, Mai, Shi-Juan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 28.04.2017
• Subjects: Bone Morphogenetic Protein 2 - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Epithelial-Mesenchymal Transition - drug effects; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Humans; Mechanistic Target of Rapamycin Complex 1 - drug effects; Mechanistic Target of Rapamycin Complex 1 - genetics; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Receptors, Cholecystokinin - biosynthesis; Research Paper; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction - drug effects; Transcriptome - genetics; Up-Regulation - drug effects; BMP2; nasopharyngeal carcinoma; metastasis; mTORC1
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101230

Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.