Ptprz1脱磷酸激活p120/β-catenin通路在口腔黏膜下纤维性变恶性转化中的作用研究

口腔黏膜下纤维性变（OSF）是一种由咀嚼槟榔引起的口腔黏膜潜在恶性疾病（OPMD）。有研究证实Ptprz1/β-catenin信号是调控肿瘤发生的重要通路，p120-catenin和β-catenin为同家族偶联体。我们前期研究发现Ptprz1为OSF恶变的特异性高表达基因，Ptprz1、p120、β-catenin在OSF和癌组织中表达递增，并发现p120异常高表达的OPMD患者恶变风险显著增加。由此我们推测Ptprz1/p120/β-catenin信号轴可能在OSF恶变中起作用，为此将进一步在大样本量人体组织中验证OSF恶变与此信号轴相关；并以槟榔碱诱导人上皮角化细胞和口腔鳞癌细胞为OSF恶变的细胞模型，阐明Ptprz1通过脱磷酸和解偶联作用分别激活p120通路和β-catenin通路促进OSF恶变的作用机制，明确其作为潜在治疗靶标的价值，为防治OSF恶变提供新的思路和实验证据。

Oral submucous fibrosis (OSF) is an oral potential malignant disease (OPMD) caused by chewing areca. Researchs have confirmed that Ptprz1/ β-catenin signaling is an important pathway in carcinogenesis, and p120-catenin and β-catenin are the same family couplets. We previously found that Ptprz1 was a highly expressed gene of OSF carcinogenesis, the expression of Ptprz1, p120 and β-catenin increased gradually in OSF and cancer tissues, and the overexpression of p120 was closely related to OPMD carcinogenesis. We hypothesized that the Ptprz1/p120/ β-catenin signal axis may play a role in OSF carcinogenesis. This project will further validate OSF carcinogenesis associated with this signal in the large sample of human tissues. OSF carcinogenesis model induced by human epithelial keratinocytes and oral squamous cell carcinoma cells by arecoline. We elucidate the mechanism of Ptprz1 promoting OSF carcinogenesis induced by arecoline by dephosphorization and uncoupling effect the activation of the p120 pathway and β-Catenin pathway for the value of potential therapeutic targets, and provide new ideas and experimental evidence for the prevention and treatment of OSF carcinogenesis.