CAJ | 학술논문

尿激酶受体（uPAR）水平升高在不同类型的浸润性肿瘤中大多可检测到，且与肿瘤预后差密切相关。尿激酶（uPA）与uPAR结合触发纤溶酶原转换成纤维蛋白溶酶，继而出现基质金属蛋白酶被激活，降低周围的细胞外基质的成分，从而促进肿瘤细胞的侵袭和转移。uPA-uPAR的相互作用会刺激细胞增殖/生存和促癌基因的表达，从而促进肿瘤的发展。除了与uPA本身的相互作用， uPAR 也与玻连蛋白之间相互作用，通过活化 Rac 和刺激细胞迁移，促进肿瘤的转移。虽然机制尚待阐明，uPAR已经显示出促进上皮-间质转化（EMT）和诱导乳腺癌肿瘤干细胞样的特性。事实上， uPAR与不同的跨膜蛋白，包括整合蛋白、G蛋白偶联受体、生长因子受体在不同肿瘤细胞的相互作用，证明 uPAR 在肿瘤发生发展中起非常关键的作用。在临床试验的早期阶段研究表明抑制肽阻止uPA-uPAR的相互作用，能延长患者的生存。uPAR的共受体在uPAR的促进肿瘤转移中的重要性表明抗癌治疗药物的发展可通过扰乱uPAR及其功能合作伴侣的相互作用。
뇨격매수체（uPAR）수평승고재불동류형적침윤성종류중대다가검측도，차여종류예후차밀절상관。뇨격매（uPA）여uPAR결합촉발섬용매원전환성섬유단백용매，계이출현기질금속단백매피격활，강저주위적세포외기질적성분，종이촉진종류세포적침습화전이。uPA-uPAR적상호작용회자격세포증식/생존화촉암기인적표체，종이촉진종류적발전。제료여uPA본신적상호작용， uPAR 야여파련단백지간상호작용，통과활화 Rac 화자격세포천이，촉진종류적전이。수연궤제상대천명，uPAR이경현시출촉진상피-간질전화（EMT）화유도유선암종류간세포양적특성。사실상， uPAR여불동적과막단백，포괄정합단백、G단백우련수체、생장인자수체재불동종류세포적상호작용，증명 uPAR 재종류발생발전중기비상관건적작용。재림상시험적조기계단연구표명억제태조지uPA-uPAR적상호작용，능연장환자적생존。uPAR적공수체재uPAR적촉진종류전이중적중요성표명항암치료약물적발전가통과우란uPAR급기공능합작반려적상호작용。
Elevated level of urokinase receptor (uPAR) is detected in various aggressive cancer types and is closely associated with poor prognosis of cancers. Binding of uPA to uPAR triggers the conversion of plasminogen to plasmin and the subsequent activation of metalloproteinases. These events confer tumor cells with the capability to degrade the components of the surrounding extracellular matrix, thus contributing to tumor cell invasion and metastasis. uPA-uPAR interaction also elicits signals that stimulate cell proliferation/survival and the expression of tumor-promoting genes, thus assisting tumor development. In addition to its interaction with uPA, uPAR also interacts with vitronectin and this interaction promotes cancer metastasis by activating Rac and stimulating cell migration. Although underlying mechanisms are yet to be fully elucidated, uPAR has been shown to facilitate epithelial-mesenchymal transition (EMT) and induce cancer stem cell-like properties in breast cancer cells. The fact that uPAR lacks intracellular domain suggests that its signaling must be mediated through its co-receptors. Indeed, uPAR interacts with diverse transmembrane proteins including integrins, ENDO180, G protein-coupled receptors and growth factor receptors in cancer cells and these interactions are proven to be critical for the role of uPAR in tumorigenesis. Inhibitory peptide that prevents uPA-uPAR interaction has shown the promise to prolong patients’ survival in the early stage of clinical trial. The importance of uPAR’s co-receptor in uPAR’s tumor-promoting effects implicate that anti-cancer therapeutic agents may also be developed by disrupting the interactions between uPAR and its functional partners.