RESUMO
Many studies have shown that FZD2 is significantly associated with tumor development and tumor metastasis. The purpose of the present study was to gain insight into the role of FZD2 in the cell proliferation and invasion of tongue squamous cell carcinoma. According to TCGA-HNSC dataset, among the 10 Frizzled receptors, FZD2 exhibited the highest degree of differential expression between cancer tissues and normal tissues, and the overall survival of patients with higher FZD2 levels was shown to be significantly shorter compared with those with lower FZD2 levels. The upregulation of FZD2 in clinical tongue cancer tissues was validated by real-time PCR. Knockdown of FZD2 inhibited the proliferation, migration and invasion of CAL-27 and TCA-8113 cells, whereas overexpression of FZD2 led to the opposite results. Further analysis revealed that FZD2 is positively correlated with WNT3A, WNT5B, WNT7A and WNT2 and is negatively correlated with WNT4. These results indicated that FZD2 may act as an oncogene in tongue squamous cell carcinoma. Therefore, FZD2 may be a target for the diagnosis, prognosis and gene therapy of tongue cancer.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Receptores Frizzled/fisiologia , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Movimento Celular , Proliferação de Células , Feminino , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Proteínas Wnt/metabolismoRESUMO
OBJECTIVES: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer. MATERIALS AND METHODS: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways. The subcutaneous tumor model was established to observe the tumor growth. RESULTS: Notch1 was upregulated in tongue carcinoma tissues and the expression of Notch1 was related with tumor stage and differentiation. Overexpression of Notch1 could increase tongue cancer cells proliferation, invasion and migration. But inhibited the expression of Notch1 could decrease cells proliferation, invasion and migration and promote cell apoptosis in vitro and in vivo. CONCLUSION: Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.