uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.
uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.
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DOI：
10.18632/oncotarget.10344
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发表时间：
2016-08-30
期刊：
影响因子：
--
通讯作者：
Mangues R
中科院分区：
文献类型：
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作者：
Pavón MA;Arroyo-Solera I;Céspedes MV;Casanova I;León X;Mangues R
有强有力的证据支持纤溶酶原激活物系统在头颈部鳞状细胞癌(HNSCC)中的作用，特别是它的uPA(尿激酶型纤溶酶原激活剂)/uPAR(尿激酶型纤溶酶原激活剂受体)和SERPINE1成分。UPA/uPAR和SERPINE1的过表达增强了肿瘤细胞的迁移和侵袭能力，在肿瘤转移过程中起关键作用，提示预后不良。通过鉴定不依赖于uPA抑制的SERPINE1激活的信号通路，解决了uPA/uPAR与其抑制剂SERPINE1产生相似作用的明显悖论。UPA/uPAR和SERPINE1均与上皮向间充质转化的诱导、干细胞特性的获得和抗肿瘤药物的耐药性直接相关。这篇综述的目的是提供关于这些蛋白质在所有这些过程中放松调控的洞察力。我们还总结了它们作为HNSCC患者预后生物标志物或潜在药物靶点的潜在价值。伴随的uPA/uPAR和SERPINE1的过度表达与较高的转移风险相关，可用于识别将从辅助治疗中受益的患者。在未来，uPA/uPAR和SERPINE1的特异性抑制剂仍在开发中，可以用来设计新的HNSCCs治疗策略。
There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes. We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs.