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蛋白酪氨酸磷酸酶O的肿瘤抑制机制及临床应用

Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications.

作者信息

Kang Man-Man, Shan Shun-Lin, Wen Xu-Yang, Shan Hu-Sheng, Wang Zheng-Jun

机构信息

The Center of Radiation Oncology, the 82th Hospital of People's Liberation Army of China, Huaian, Jiangsu, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(15):6215-23. doi: 10.7314/apjcp.2015.16.15.6215.

Abstract

Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor- suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

摘要

酪氨酸磷酸化在调节人类生理和病理过程中发挥着重要作用。酪氨酸磷酸化的功能稳定在很大程度上有助于蛋白质酪氨酸激酶(PTK)和蛋白质酪氨酸磷酸酶(PTP)的平衡、协调调节。研究表明,PTP通过逆转癌蛋白功能在肿瘤发生和进展中发挥重要的抑制作用。受体型蛋白酪氨酸磷酸酶O(PTPRO)作为PTP家族的一员,也被发现在肿瘤发展中具有一定作用。一些报道显示,肿瘤中PTPRO的过表达不仅可以抑制肿瘤细胞分裂频率、诱导肿瘤细胞死亡,还能抑制迁移。然而,肿瘤抑制机制非常复杂且尚未完全明确,这在一定程度上阻碍了PTPRO的进一步发展。因此,为了解决这个问题,我们在此总结了研究结果以得出有意义的结论。我们发现PTPRO的肿瘤抑制机制多种多样,如控制肿瘤细胞增殖周期的G0/G1期、抑制底物磷酸化、下调转录激活因子等。在临床抗癌工作中,肿瘤中PTPRO的表达水平不仅可以作为监测患者预后的生物标志物,还能作为无创诊断的表观遗传生物标志物。此外,肿瘤组织中PTPRO的重新激活不仅可以诱导肿瘤体积缩小,还能增强对化疗药物的敏感性。所以,我们可以提出,PTPRO的这些研究结果不仅将为其他肿瘤抑制因子提供新的研究思路和方向,重要的是,还将为未来研究新型分子靶向药物提供理论基础。

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