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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

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

Takahiro Chiba, Akira Ishisaki, Seiko Kyakumoto, Toshiyuki Shibata, Hiroyuki Yamada, Masaharu Kamo

Oncol Rep. 2017 Feb;37(2):713-720.

PMID: 28035402

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248565	Bone Morphogenetic Protein 4 human			Price

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