Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.
Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.
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DOI：
10.2174/1381612823666170616082125
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发表时间：
2017-11-16
影响因子：
3.1
通讯作者：
Kim DJ
中科院分区：
文献类型：
--
作者：
Kim M;Baek M;Kim DJ
蛋白质酪氨酸磷酸化是一种重要的信号传导机制，在上皮细胞癌变过程中发挥作用。蛋白酪氨酸激酶（PTKs）通过激活包括STAT 3、AKT和MAPK在内的主要信号通路来控制包括生长、分化、代谢和运动在内的各种细胞过程。PTKs的基因突变和/或PTKs及其下游通路的长期激活可导致上皮癌的发展。因此，PTKs成为一个有吸引力的癌症预防靶点。PTK抑制剂正在不断开发中，目前用于治疗显示PTK高表达的癌症。蛋白酪氨酸磷酸酶（PTPs），PTKs的稳态对应物，负调节磷酸酪氨酸信号传导的速率和持续时间。PTP最初被认为只是具有低特异性的管家酶。然而，最近的研究表明，PTPs可以作为肿瘤抑制剂或肿瘤促进剂，这取决于其靶底物。PTK和PTP信号转导途径是癌症预防和治疗的潜在治疗靶点。
Protein tyrosine phosphorylation is a crucial signaling mechanism that plays a role in epithelial carcinogenesis. Protein tyrosine kinases (PTKs) control various cellular processes including growth, differentiation, metabolism, and motility by activating major signaling pathways including STAT3, AKT, and MAPK. Genetic mutation of PTKs and/or prolonged activation of PTKs and their downstream pathways can lead to the development of epithelial cancer. Therefore, PTKs became an attractive target for cancer prevention. PTK inhibitors are continuously being developed, and they are currently used for the treatment of cancers that show a high expression of PTKs. Protein tyrosine phosphatases (PTPs), the homeostatic counterpart of PTKs, negatively regulate the rate and duration of phosphotyrosine signaling. PTPs initially were considered to be only housekeeping enzymes with low specificity. However, recent studies have demonstrated that PTPs can function as either tumor suppressors or tumor promoters, depending on their target substrates. Together, both PTK and PTP signal transduction pathways are potential therapeutic targets for cancer prevention and treatment.