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

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.

• Publication year

  2017

• Venue

  Aging

• Publication date

  2017-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/aging.101230PMID 28455969PMCID 5425130
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The role of bone morphogenetic proteins in ovarian function.

  2019cited by this paper
• Bone metastasis risk factors in breast cancer

  2017cited by this paper
• Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

  2016cited by this paper
• Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

  2016cited by this paper
• Promotive effects of bone morphogenetic protein 2 on angiogenesis in hepatocarcinoma via multiple signal pathways

  2016cited by this paper
• Recombinant Human Bone Morphogenetic Protein-2 in Development and Progression of Oral Squamous Cell Carcinoma.

  2016cited by this paper
• BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas

  2016cited by this paper
• Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway

  2016cited by this paper
• Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

  2016cited by this paper
• C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer

  2015cited by this paper
• RETRACTED ARTICLE: Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer

  2015cited by this paper
• BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

  2015cited by this paper
• Bone morphogenetic protein 2 inhibits hepatocellular carcinoma growth and migration through downregulation of the PI3K/AKT pathway

  2014cited by this paper
• Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: treatment outcomes of a prospective, multicentric clinical study.

  2014cited by this paper
• Activation of Akt/mTOR Pathway Is Associated with Poor Prognosis of Nasopharyngeal Carcinoma

  2014cited by this paper
• Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities.

  2014cited by this paper
• Bone Morphogenetic Proteins: structure, biological function and therapeutic applications.

  2014cited by this paper
• Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells

  2014cited by this paper
• Silencing BMP-2 expression inhibits A549 and H460 cell proliferation and migration

  2014cited by this paper
• Activated NF-κB in Bone Marrow Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients Inhibits Osteogenic Differentiation Through Downregulating Smad Signaling

  2013cited by this paper
• Regulation of EMT by Notch signaling pathway in tumor progression.

  2013cited by this paper
• Serum BMP-2 up-regulation as an indicator of poor survival in advanced non-small cell lung cancer patients.

  2013cited by this paper
• Bi‐directional roles of bone morphogenetic proteins in cancer: Another molecular Jekyll and Hyde?

  2013cited by this paper
• Expression of bone-morphogenetic protein 2 and tumor necrosis factor α correlates with bone metastases in bladder urothelial carcinoma.

  2013cited by this paper
• Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre.

  2013cited by this paper
• Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2.

  2013cited by this paper
• The mTOR Signalling Pathway in Human Cancer

  2012cited by this paper
• mTOR signaling in growth control and disease.

  2012cited by this paper
• The serum bone morphogenetic protein-2 level in non-small-cell lung cancer patients

  2012cited by this paper
• Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: A meta-analysis of clinical evidence

  2012cited by this paper
• Activation of AKT is associated with metastasis of nasopharyngeal carcinoma

  2012cited by this paper
• TGF-β-induced activation of mTOR complex 2 drives epithelial–mesenchymal transition and cell invasion

  2012cited by this paper
• Focus Issue: TOR Signaling, a Tale of Two Complexes

  2012cited by this paper
• BMP signaling in vascular diseases

  2012cited by this paper
• Familial and large-scale case-control studies identify genes associated with nasopharyngeal carcinoma.

  2012cited by this paper
• Lung Tumor-associated Osteoblast-derived Bone Morphogenetic Protein-2 Increased Epithelial-to-Mesenchymal Transition of Cancer by Runx2/Snail Signaling Pathway*

  2011cited by this paper
• The prevalence and prevention of nasopharyngeal carcinoma in China

  2011cited by this paper
• BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line

  2011cited by this paper
• Activation of the PI3K/Akt Pathway Mediates Bone Morphogenetic Protein 2-Induced Invasion of Pancreatic Cancer Cells Panc-1

  2011cited by this paper
• Metastatic function of BMP-2 in gastric cancer cells: the role of PI3K/AKT, MAPK, the NF-κB pathway, and MMP-9 expression.

  2011cited by this paper
• Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism

  2011cited by this paper
• mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.

  2011cited by this paper
• Independent and cooperative roles of tumor necrosis factor‐α, nuclear factor‐κB, and bone morphogenetic protein‐2 in regulation of metastasis and osteomimicry of prostate cancer cells and differentiation and mineralization of MC3T3‐E1 osteoblast‐like cells

  2010cited by this paper
• Bone Morphogenetic Proteins and Cancer: Review of the Literature

  2010cited by this paper
• Bone morphogenetic proteins in breast cancer: dual role in tumourigenesis?

  2010cited by this paper
• Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression

  2010cited by this paper
• p38 Regulates Expression of Osteoblast-specific Genes by Phosphorylation of Osterix*

  2010cited by this paper
• BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

  2010cited by this paper
• Nasopharyngeal carcinoma: the next challenges.

  2010cited by this paper
• BMP‐2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway

  2008cited by this paper
• Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway

  2008cited by this paper
• Targeting the mTOR signaling network in cancer.

  2007cited by this paper
• A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7

  2007cited by this paper
• Bone Morphogenetic Protein-2–Induced Transformation Involves the Activation of Mammalian Target of Rapamycin

  2005cited by this paper
• Expression of bone morphogenetic protein 2 in breast cancer cells inhibits hypoxic cell death.

  2005cited by this paper
• The BMP signaling and in vivo bone formation.

  2005cited by this paper
• Nasopharyngeal carcinoma.

  2005cited by this paper
• Bone Morphogenetic Proteins

  2004cited by this paper
• Increased expression of bone morphogenetic protein‐7 in bone metastatic prostate cancer

  2003cited by this paper
• Mechanisms of TGF-beta signaling from cell membrane to the nucleus.

  2003cited by this paper
• Requirement of BMP-2-induced Phosphatidylinositol 3-Kinase and Akt Serine/Threonine Kinase in Osteoblast Differentiation and Smad-dependent BMP-2 Gene Transcription*

  2002cited by this paper
• Smads: transcriptional activators of TGF-beta responses.

  1998cited by this paper
• Bone morphogenetic proteins in development.

  1996cited by this paper
• The bone morphogenetic protein family and osteogenesis

  1992cited by this paper
• Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro

  1991cited by this paper
• Nasopharyngeal carcinoma: the significance of neck node involvement in relation to the pattern of distant failure.

  1990cited by this paper

• ELAVL1-Regulated Bone Morphogenetic Protein 2 as a Predictive Biomarker for Ultrasound Therapy Response in Oral Squamous Cell Carcinoma Bone Infiltration.

  2025cites this paper
• Bone morphogenetic protein 2 rescues neurogenic abnormalities and angiogenic factors in mice with bilateral cavernous nerve injury.

  2025cites this paper
• Exosomal 4EBP1 promotes head and neck cancer progression via regulating mitochondrial fission.

  2025cites this paper
• mTORC1 regulates the proliferation of SOX9+ porcine skin-derived stem cells (pSDSCs) by promoting S6K phosphorylation

  2025influential citation
• L-tetrahydropalmatine attenuates methamphetamine-induced pulmonary vascular remodeling via CaSR-BMP2/mTOR signaling.

  2025cites this paper
• Dihydroalterperylenol from endophytic fungus Alternaria semiverrucosa and its antitumour activity uncovered by transcriptome analysis, molecular docking and molecular dynamics simulations

  2025cites this paper
• SOX9 promotes stemness in the CAL27 cell line of tongue squamous cell carcinoma

  2024cites this paper
• Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single‐cell transcriptomics

  2024cites this paper
• Mechanisms of Bone Morphogenetic Protein 2 in Respiratory Diseases

  2024cites this paper
• Methods of improving the surface of endoprostheses based on titanium alloys used in pediatric oncology.

  2024cites this paper
• Cellular senescence by loss of Men1 in osteoblasts is critical for age‐related osteoporosis

  2024cites this paper
• RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway

  2024cites this paper
• MicroRNA 211-5p inhibits cancer cell proliferation and migration in pancreatic cancer by targeting BMP2

  2023cites this paper
• Association between the expression levels of ADAMTS16 and BMP2 and tumor budding in hepatocellular carcinoma

  2023cites this paper
• Selective targeting BMP2 and 4 in SMAD4 negative esophageal adenocarcinoma inhibits tumor growth and aggressiveness in preclinical models

  2022cites this paper
• BMP2 as a promising anticancer approach: functions and molecular mechanisms

  2022cites this paper
• Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

  2022cites this paper
• Molecular mechanism of FBXW7-mediated ubiquitination modification in nasopharyngeal carcinoma cell proliferation in vitro and in vivo.

  2022cites this paper
• BMP2 increases hyperplasia and hypertrophy of bovine subcutaneous preadipocytes via BMP/SMAD signaling

  2022cites this paper
• The role of miR-370 and miR-138 in the regulation of BMP2 suppressor gene expression in colorectal cancer: preliminary studies

  2022cites this paper
• Regulatory mechanism of lncRNA CTBP1-AS2 in nasopharyngeal carcinoma cell proliferation and apoptosis via the miR-140-5p/BMP2 axis.

  2022cites this paper
• Identification of Novel Kinase–Transcription Factor–mRNA–miRNA Regulatory Network in Nasopharyngeal Carcinoma by Bioinformatics Analysis

  2021cites this paper
• Inhibition of Bone Morphogenetic Protein 2 Suppresses the Stemness Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma via the MAPK/ERK Pathway

  2021cites this paper
• Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both β-catenin and NF-κB

  2021cites this paper
• LMO2 is critical for early metastatic events in breast cancer

  2021cites this paper
• A tale of two multi‐focal therapies for glioblastoma: An antibody targeting ELTD1 and nitrone‐based OKN‐007

  2021cites this paper
• Role of Apelin/APJ axis in cancer development and progression.

  2020cites this paper
• A strategy for the identification of paracrine regulators of cancer cell migration

  2020cites this paper
• Bone morphogenetic protein 2 (BMP2) mediates spermatogenesis in Chinese mitten crab Eriocheir sinensis by regulating kinesin motor KIFC1 expression.

  2020cites this paper
• Rab1A promotes cancer metastasis and radioresistance through activating GSK-3β/Wnt/β-catenin signaling in nasopharyngeal carcinoma

  2020cites this paper
• Construction and characterization of an adenoviral vector encoding human bone morphogenetic protein-2

  2020cites this paper
• BMP2 variants in the risk of ankylosing spondylitis

  2019cites this paper
• ACVR1 Function in Health and Disease

  2019cites this paper
• Cancer Conditioned Medium Modulates Functional and Phenotypic Properties of Human Decidua Parietalis Mesenchymal Stem/Stromal Cells

  2019cites this paper
• mTOR: Role in cancer, metastasis and drug resistance.

  2019cites this paper
• SOX9 promotes nasopharyngeal carcinoma cell proliferation, migration and invasion through BMP2 and mTOR signaling.

  2019cites this paper
• Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication

  2019cites this paper
• Effects of microRNA-378 on epithelial-mesenchymal transition, migration, invasion and prognosis in gastric carcinoma by targeting BMP2.

  2019cites this paper
• Quantitative analysis of BMP-2 derived peptide covalently grafted onto oxidized detonation nanodiamonds

  2019cites this paper
• Improved osseointegration with rhBMP-2 intraoperatively loaded in a specifically designed 3D-printed porous Ti6Al4V vertebral implant.

  2019cites this paper
• Silencing of Long Non-coding RNA SMAD5-AS1 Reverses Epithelial Mesenchymal Transition in Nasopharyngeal Carcinoma via microRNA-195-Dependent Inhibition of SMAD5

  2019influential citation
• Bioengineering The Fracture Callus: Bone Repair Through Fracture Mimetics

  2019cites this paper
• Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis

  2018cites this paper
• The effect of Mg‑2Zn‑0.5Nd alloy on the mTOR signalling pathway in L6 cells.

  2018cites this paper
• Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents Trauma-Induced Heterotopic Ossification.

  2017cites this paper