Bone morphogenetic protein-4-induced epithelial-mesenchymal transition and invasiveness through Smad1-mediated signal pathway in squamous cell carcinoma of the head and neck
| Autor: | Jin-jie Sun, Xin Zhang, Leiming Pi, Ting Xu, Changyun Yu, Yongquan Tian, Xingwei Wang, Yong Liu |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty animal structures Epithelial-Mesenchymal Transition Cell Gene Expression Vimentin Bone Morphogenetic Protein 4 Kaplan-Meier Estimate Bone morphogenetic protein Disease-Free Survival Metastasis Smad1 Protein Cell Movement Cell Line Tumor Carcinoma medicine Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Neoplasms Squamous Cell Cell Shape Gene knockdown biology Squamous Cell Carcinoma of Head and Neck General Medicine medicine.disease Cadherins Prognosis stomatognathic diseases medicine.anatomical_structure Bone morphogenetic protein 4 Head and Neck Neoplasms embryonic structures biology.protein Cancer research Carcinoma Squamous Cell RNA Interference Follow-Up Studies Signal Transduction |
| Zdroj: | Archives of medical research. 42(2) |
| ISSN: | 1873-5487 |
| Popis: | Background and Aims Bone morphogenetic proteins (BMPs) have recently been shown to be involved in the genesis and progression of a wide variety of carcinomas. The present study was undertaken to estimate the effect of BMP-4 on squamous cell carcinoma of the head and neck (SCCHN) in tissue and cell levels. Methods In this study, immunohistochemistry, Western blotting and RT-PCR were utilized to detect the expression of BMP-4, Smad1 and phosphorylated Smad1 in SCCHN tissues or SCCHN cell lines. Those three proteins in tissues were further correlated with prognosis of SCCHN by Kaplan-Meier analysis. The epithelial-mesenchymal transition (EMT)-associated changes in SCCHN cells were detected after stimulation by human BMP-4 recombinant protein and knockdown of Smad1 gene. Meanwhile, the effect on invasiveness and migration was evaluated by invasion and scratch assays, respectively. Results BMP-4 and p-Smad1 protein were overexpressed in SCCHN tissues with cervical lymph node metastasis, which was significantly higher than those without metastasis. The expression of BMP-4 and p-Smad1 protein was negatively correlated with the prognosis of SCCHN. BMP-4 promoted the invasiveness and migration through EMT, which was demonstrated by morphological alterations, loss of E-cadherin, increase of vimentin and activation of the Smad1 signal pathway. Knockdown of Smad1 expression suppressed BMP-4 induced EMT in both cell lines and weakened the invasiveness and migration of Tu686 and Tu212 in vitro . Conclusions Our results demonstrate that BMP-4 protein may contribute to the malignant metastasis of SCCHN, which presents as a novel prognostic marker and a potential therapeutic target for patients with SCCHN. |
| Databáze: | OpenAIRE |
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