TXNDC12通过上调β-catenin促进肝癌转移的分子机制研究

Metastasis is one of the main reasons that contribute to poor prognosis of hepatocellular carcinoma (HCC). Previously, we have found that TXNDC12 is a potential oncogene, which might promote the metastasis of liver cancer. Based on the immunohistochemical (IHC) quantification data of clinical HCC samples, we found that high levels of TXNDC12 expression were correlated with poorly differentiated tumors, more frequent vascular invasion and poor prognosis. WNT/β-catenin pathway plays a key regulatory role in tumor metastasis. Our preliminary work showed that TXNDC12 could directly interact with β-catenin, which then translocated into nucleus and promoted epithelial-mesenchymal transition (EMT) and metastasis. In this project, we will utilize the mice model to evaluate the effect of TXNDC12 overexpression/knockdown on liver cancer metastasis. Additionally, we will illustrate the molecular mechanism of TXNDC12 on WNT/β-catenin pathway and EMT process. Moreover, we will enlarge the clinical sample size to analyze the potential prognostic value of TXNDC12 and β-catenin. Our study will benefit the evaluation of TXNDC12 and β-catenin as potential prognostic factors of HCC.

肿瘤转移是导致肝癌患者不良预后的重要原因。前期我们通过蛋白质组学分析筛选并验证了二硫键异构酶TXNDC12在高转移潜能的肝癌细胞中高表达。结合患者临床数据和随访信息的分析显示，TXNDC12的表达水平与肿瘤分化、血管侵犯、患者预后等密切相关。WNT/β-catenin信号通路是肿瘤转移过程中的关键调控通路。前期结果提示TXNDC12可能直接通过与β-catenin相互作用，促进β-catenin入核，进而诱导EMT和肿瘤转移。在此基础上，本项目拟结合动物模型评价TXNDC12与β-catenin对肝癌转移的影响；阐明TXNDC12对WNT/β-catenin信号通路的调控机制；扩大临床样本量，明确TXNDC12 与β-catenin在肝癌中的病理学意义。通过本课题的实施，有望明确 TXNDC12与β-catenin 作为肝癌生物标记物或药物靶标的潜在应用价值，为后续转化医学研究奠定基础。

肿瘤转移是导致肝癌患者不良预后的重要原因。前期我们通过蛋白质组学分析筛选并验证了二硫键异构酶TXNDC12在高转移潜能的肝癌细胞中高表达。结合患者临床数据和随访信息的分析显示，TXNDC12的表达水平与肿瘤分化、血管侵犯、患者预后等密切相关。WNT/β-catenin信号通路是肿瘤转移过程中的关键调控通路。前期结果提示TXNDC12可能直接通过与β-catenin相互作用，促进β-catenin入核，进而诱导EMT和肿瘤转移。在此基础上，本项目结合动物模型评价了TXNDC12与β-catenin对肝癌转移的影响；阐明了TXNDC12对WNT/β-catenin信号通路的调控机制；扩大临床样本量，明确了TXNDC12 与β-catenin在肝癌中的病理学意义。通过本课题的实施，明确了 TXNDC12与β-catenin 作为肝癌生物标记物和药物靶标的潜在应用价值，为后续转化医学研究奠定了基础。