ArticleCancer science2013
Bone morphogenetic protein-9 induces epithelial to mesenchymal transition in hepatocellular carcinoma cells.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Bone morphogenetic protein (BMP)-9, a systemic homeostasis factor with diverse functions in the liver and beyond.Bioscience reports · 2025Review
- A Comprehensive Review Exploring the Role of Bone Morphogenetic Proteins [BMP]: Biological Mechanisms.Current issues in molecular biology · 2025Review
- Unveiling the Impact of BMP9 in Liver Diseases: Insights into Pathogenesis and Therapeutic Potential.Biomolecules · 2024Review
- Addition of heparin binding sites strongly increases the bone forming capabilities of BMP9Bioactive materials · 2023Article
- BMP9 maintains the phenotype of HTR-8/Svneo trophoblast cells by activating the SDF1/CXCR4 pathway.BMC molecular and cell biology · 2023Article
- BMP signaling inhibition overcomes chemoresistance of prostate cancer.American journal of cancer research · 2023Article
- Article
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- Genome-wide identification, characterization and expression analysis of the BMP family associated with beak-like teeth inFrontiers in genetics · 2022Article
- Effects of bone morphogenetic proteins on epithelial repair.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- The Dual Effect of the BMP9-ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?Cancers · 2021Review
- New insights into BMP9 signaling in liver diseases.Molecular and cellular biochemistry · 2021Review
- Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signalingExperimental and therapeutic medicine · 2021Article
- Potential roles of bone morphogenetic protein-9 in glucose and lipid homeostasis.Journal of physiology and biochemistry · 2020Review
- A Signaling Crosstalk between BMP9 and HGF/c-Met Regulates Mouse Adult Liver Progenitor Cell Survival.Cells · 2020Article
- BMP-9 is a novel marker for colorectal tumorigenesis undergoing the normal mucosa-adenoma-adenocarcinoma sequence and is associated with colorectal cancer prognosis.Oncology letters · 2020Article
- Differential Consequences ofCells · 2019Article
- The wonders of BMP9: From mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine.Genes & diseases · 2019Review
- Adenovirus‑mediated overexpression of bone morphogenetic protein‑9 promotes methionine choline deficiency‑induced non‑alcoholic steatohepatitis in non‑obese mice.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) is an important mechanism to initiate cancer invasion and metastasis. Bone morphogenetic protein (BMP)-9 is a member of the transforming growth factor (TGF)-β superfamily. It has been suggested to play a role in cancer development in some non-hepatic tumors. In the present study, two hepatocellular carcinoma (HCC) lines, HLE and HepG2, were treated with BMP-9 in vitro, and phenotypic changes and cell motility were analyzed. In situ hybridization (ISH) and immunohistochemical analyses were performed with human HCC tissue samples in order to assess expression levels of BMP-9. In vivo, BMP-9 protein and mRNA were expressed in all the tested patients to diverse degrees. At the protein level, mildly positive (1 + ) BMP-9 staining could be observed in 25/41 (61%), and moderately to strongly positive (2 + ) in 16/41 (39%) of the patients. In 27/41 (65%) patients, the BMP-9 protein expression level was consistent with the mRNA expression level as measured by ISH. In those patients with 2 + protein level, nuclear pSmad1 expression in cancer cells was also significantly increased. Expression of BMP-9 was positively related to nuclear Snail expression and reversely correlated to cell surface E-cadherin expression, although this did not reach statistical significance. Expression levels of BMP-9 were significantly associated with the T stages of the investigated tumors and high levels of BMP-9 were detected by immunofluorescence especially at the tumor borders in samples from an HCC mouse model. In vitro, BMP-9 treatment caused a reduction of E-cadherin and ZO-1 and an induction of Vimentin and Snail expression. Furthermore, cell migration was enhanced by BMP-9 in both HCC cell lines. These results imply that EMT induced by BMP-9 is related to invasiveness of HCC.
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