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.
Highlights
Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian population
The protein expression level of Bone morphogenetic protein‐2 (BMP2) was obviously higher in S-18 and 5-8F cells with high tumorigenic and metastatic potential compared with their paired subclones S-26 and 6-10B cell lines with low tumorigenic and metastatic potential (Fig. 1B)
In our previous study with aim to characterize aberrant transcript expression that contribute to the NPC oncogenesis, RNA sequencing (RNA-seq) was performed to discriminate gene expression profiles in NPC cell lines CNE2 and C666-1 and an immortalized nasopharyngeal epithelial cell line NP69 using an Illumina Hiseq 2500 platform. 1323 and 1106 differentially expressed mRNAs (p < 0.05) were identified in C666-1 and CNE2 www.aging‐us.com cells when compared with NP69 cells, respectively
Summary
Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian population. NPC has the highest metastasis features among head and neck cancers, with approximately 75–85% of patients have regional lymph node metastasis, and 15-19% of patients develop distant metastasis [4, 5]. NPC is sensitive to radiotherapy (RT) and the addition of chemotherapy to RT works effectively, treatment failure for NPC remains quite frequent, with rate of approximately 20% for distant metastasis [6, 7]. The prognosis for NPC is still poor with a 5-year survival rate range from 50% to 70% for patients in advanced stage [8]. More than 20 BMPs have been identified in humans. Discovered by their ability to induce formation and development of bone and cartilage, these www.aging‐us.com
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