Research Paper Volume 9, Issue 4 pp 1326—1340
BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway
- 1 State Key Laboratory of Oncology in South China, Guangzhou, 510060, China
- 2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
- 3 Zhoukou Hospital of Traditional Chinese Medicine, Zhoukou, China
- 4 Cancer Center of Guangzhou Medical University, Guangzhou, China
- 5 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08901, USA
Received: March 14, 2017 Accepted: April 23, 2017 Published: April 28, 2017
https://doi.org/10.18632/aging.101230How to Cite
Abstract
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.