Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China.
Center of Scientific Research, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China.
Mol Cancer. 2020 Jan 4;19(1):2. doi: 10.1186/s12943-019-1124-x.
The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.
核斑型痘病毒和锌指（POZ）蛋白（SPOP），作为泛素连接酶 Cullin-RING E3 的代表性底物识别亚基，已被证实具有在肿瘤发生和癌症进展中发挥双重作用的特点。大量研究表明，SPOP 抑制多种人类恶性肿瘤的发生，如前列腺癌、肺癌、结肠癌、胃癌和肝癌。然而，一些研究表明 SPOP 在肾癌中具有致癌功能，这表明 SPOP 可以以癌症类型特异性的方式发挥其生物学功能。SPOP 在甲状腺癌、宫颈癌、卵巢癌、骨癌和神经癌中的作用尚未确定。在这篇综述文章中，我们描述了 SPOP 在人类癌症中的结构和调节。此外，我们基于三个主要类别（生理证据（动物模型）、病理证据（人类癌症标本）和生化证据（下游泛素底物））强调了 SPOP 在肿瘤发生中的关键作用。此外，我们注意到 SPOP 可能是癌症治疗有前途的治疗靶点。
