SPOP蛋白在肾细胞癌中的表达及其功能的研究进展

Research update of SPOP expression and its oncological functions in renal cell carcinoma

肾细胞癌(肾癌)约占肾恶性肿瘤的85%,肾透明细胞癌是肾癌最常见的组织亚型,早期往往缺乏临床表现,多数被诊断为肾细胞癌的患者已到了肾癌晚期。早期肾癌的患者通过根治性肾切除术可以达到较好的治愈效果。晚期肾癌具有多药物耐药基因,对放化疗均不敏感,目前仍没有理想的治疗手段;靶向治疗是晚期肾癌的一线治疗方案,但长期使用靶向药物后容易出现耐药及相关的不良反应。因此,迫切需要探索肾癌的敏感生物标志物和特异性治疗靶点。SPOP蛋白作为E3泛素连接酶CUL-3的接头分子,能与肿瘤细胞中的多种蛋白结合,促使靶蛋白发生泛素化和降解。以往的研究发现,SPOP蛋白在肾癌细胞胞质中呈过表达状态,特别是在肾透明细胞癌中高度表达,并可能通过对肾癌细胞中的肿瘤相关因子,如抑癌因子PTEN、死亡结构域相关蛋白DAXX等进行泛素化和降解发挥促癌作用。在本文中,我们将对SPOP蛋白在肾癌中的表达及其分子功能的研究进展作以下综述。

Renal cell carcinoma(RCC)accounts for about 85%of renal malignant tumors,renal clear cell carcinoma is the most common pathological pattern of renal cancer,which often shows asymptomatic in the early stage.Most patients of RCC were diagnosed with late stage.Early stage RCC could be cured by radical nephrectomy.However,there was no satisfactory treatment yet for local advanced and metastatic RCC.Targeted therapy was currently first-line treatment for late stage renal carcinoma.Advanced RCC had multiple drug resistance genes which was insensitive to radiotherapy or chemotherapy.In addition,side effects and drug resistance were also problems which need to be further solved.Taken together,finding the sensitive predictors and effective therapeutic targets for RCC was a challenge for scientists.SPOP protein,known as the connector molecule of the E3 ubiquitin ligase CUL-3,could bind to lots of proteins in tumor cells and promote the ubiquitination and degradation of the target proteins.Previous studies demonstrated that SPOP protein was overexpressed in the cytoplasm of RCC,especially in ccRCC,and might play an important role in tumorigenesis and aggression through ubiquitination and degradation of tumor-related factors in renal cancer cells,such as tumor suppressor PTEN and death domain associated protein DAXX.The research update of SPOP expression and its oncological functions in renal cell carcinoma were reviewed in this manuscript.