AR/ITGB5/PTEN信号轴促进前列腺癌细胞上皮间充质转换的机制研究

Prostate cancer is a common malignancy in urinary system. Due to the disadvantages and limitation of PSA in clinical diagnosis, novel diagnostic serum biomarkers are urgently needed. By highthrough-put screening, we identified the combination of three genes (ITGB5, TIMP1, TMEM176B) have higher sensitivity and accuracy when compared to traditional biomarker PSA. Based on the clinical samples, we found that ITGB5 was highly expressed in the serum as well as the tumor tissues from prostate cancer patients. Subsequent experiments demonstrated that AR can activate the transcription of ITGB5 and ITGB5 promotes epithelial to mesenchymal transition by interacting with PTEN. Thus, we proposed that AR/ITGB5/PTEN axis plays a vital role in mediating epithelial to mesenchymal transition and cancer metastasis. We aim to use cell line and animal model as well as clinical specimens to characterize the function of ITGB5 in prostate cancer. We also would like to reveal the molecular mechanisms of AR/ITGB5/PTEN axis in cancer metastasis, which can shed light on the development of novel diagnostic marker and the underlying mechanisms of prostate cancer.

前列腺癌是泌尿系统最常见的恶性肿瘤之一。鉴于临床PSA筛查诊断的局限性，新的前列腺癌血清学诊断标记物仍有待开发。通过芯片的高通量筛选，我们发现三基因（ITGB5、TIMP1、TMEM176B）联合诊断比传统PSA具有更高的敏感性和特异性。临床样本研究发现，ITGB5在前列腺癌患者的外周血和癌组织中均高表达。进一步的细胞和分子水平实验表明雄激素受体（AR）能激活ITGB5的转录，同时ITGB5通过与PTEN相互作用从而促进前列腺癌细胞的上皮间充质转换。因此，我们提出AR/ITGB5/PTEN信号轴在前列腺癌上皮间充质转换以及肿瘤的转移过程中起着重要作用。本项目拟通过各种细胞模型及动物实验，结合临床样本，明确ITGB5在前列腺癌中的表达及意义，同时揭示AR/ITGB5/PTEN信号轴在肿瘤细胞转移中的分子机制，为阐述前列腺癌的早期诊断及分子发病机制提供新的理论依据。

前列腺癌是泌尿系统最常见的恶性肿瘤之一。鉴于临床PSA筛查诊断的局限性，新的前列腺癌血清学诊断标记物仍有待开发。通过芯片的高通量筛选，我们发现三基因（ITGB5、TIMP1、TMEM176B）联合诊断比传统PSA具有更高的敏感性和特异性。临床样本研究发现，ITGB5在前列腺癌患者的外周血和癌组织中均高表达。进一步的细胞和分子水平实验表明雄激素受体（AR）能激活ITGB5的转录，同时ITGB5通过与PTEN相互作用从而促进前列腺癌细胞的上皮间充质转换。因此，我们提出AR/ITGB5/PTEN信号轴在前列腺癌上皮间充质转换以及肿瘤的转移过程中起着重要作用。本项目通过各种细胞模型及动物实验，结合临床样本，明确ITGB5在前列腺癌中的表达及意义，同时揭示AR/ITGB5/PTEN信号轴在肿瘤细胞转移中的分子机制，为阐述前列腺癌的早期诊断及分子发病机制提供新的理论依据。