Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression
| Autor: | Seiko Kyakumoto, Toshiyuki Shibata, Takahiro Chiba, Masaharu Kamo, Hiroyuki Yamada, Akira Ishisaki |
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| Rok vydání: | 2016 |
| Předmět: |
mesenchymal-epithelial transition
squamous cell carcinoma Smad5 Protein 0301 basic medicine Cancer Research Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Blotting Western Bone Morphogenetic Protein 2 Apoptosis Smad Proteins Biology Real-Time Polymerase Chain Reaction Bone morphogenetic protein 2 Smad1 Protein Transforming Growth Factor beta1 03 medical and health sciences Cell Movement Tumor Cells Cultured medicine metastasis Humans Mesenchymal–epithelial transition RNA Messenger Epithelial–mesenchymal transition Smad Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Cell growth ID1 transforming growth factor-β Articles General Medicine Cell cycle Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Smad8 Protein embryonic structures Cancer cell Carcinoma Squamous Cell Cancer research bone morphogenetic protein-2 Mouth Neoplasms A431 cells Transforming growth factor |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Squamous cell carcinoma is the most common cancer in the oral cavity. We previously demonstrated that transforming growth factor-β1 (TGF-β1) promotes the epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (hOSCC) cells; however, it remains to be clarified whether the TGF-β superfamily member bone morphogenetic protein (BMP) affects this process in hOSCC cells. Here, we examined the independent and collective effects of TGF-β1 and BMP-2 on EMT and mesenchymal‑epithelial transition (MET) in a panel of four hOSCC cell lines. Notably, we found that HSC-4 cells were the most responsive to BMP-2 stimulation, which resulted in the upregulation of Smad1/5/9 target genes such as the MET inducers ID1 and cytokeratin 9 (CK9). Furthermore, BMP-2 downregulated the mesenchymal marker N-cadherin and the EMT inducer Snail, but upregulated epithelial CK9 expression, indicating that BMP-2 prefers to induce MET rather than EMT. Moreover, TGF-β1 dampened BMP-2-induced epithelial gene expression by inhibiting Smad1/5/9 expression and phosphorylation. Functional analysis revealed that TGF-β1 and BMP-2 significantly enhanced HSC-4 cell migration and proliferation, respectively. Collectively, these data suggest that TGF-β positively regulates hOSCC invasion in the primary tumor, whereas BMP-2 facilitates cancer cell colonization at secondary metastatic sites. Thus, the invasive and metastatic characteristics of hOSCC appear to be reciprocally regulated by BMP and TGF-β. |
| Databáze: | OpenAIRE |
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