SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma

Yan Pu, Jing Han, Mengmeng Zhang, Mengxue Liu, Gulnazar Abdusamat, Hui-Bin Liu
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引用次数: 1

Abstract

The most hostile form of urologic cancer, clear cell renal cell carcinoma (ccRCC), has a high fatality rate and poor prognosis due to tumor metastasis at initial presentation. The complex process driving ccRCC metastasis is still unknown, though. In this study, we demonstrate that Spindle and kinetochore-associated protein 1 (SKA1) expression is significantly upregulated in ccRCC tissues and associated with aggressive clinicopathologic characteristics. Functionally, SKA1 knockdown on ccRCC cells reduced cancer cell motility both in vivo and in vitro research. These bioactivities of SKA1 may be brought on by its specific interaction with scaffold attachment factor B, according to the proposed mechanism (SAFB), which could further depress the transcription of dual specificity phosphatase 6 (DUSP6). Our findings may provide a new way of researching SKA1-regulated tumor metastasis, and indicate that SKA1 is a prospective therapeutic target for renal carcinoma.
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在透明细胞肾细胞癌中,SKA1通过safb介导的DUSP6转录抑制促进肿瘤转移
透明细胞肾细胞癌(clear cell renal cell carcinoma, ccRCC)是泌尿系统癌症中最具敌意的一种,由于最初出现肿瘤转移,死亡率高,预后差。然而,驱动ccRCC转移的复杂过程仍然未知。在这项研究中,我们证明纺锤体和着丝酶相关蛋白1 (SKA1)表达在ccRCC组织中显著上调,并与侵袭性临床病理特征相关。在体内和体外研究中,SKA1敲低ccRCC细胞的功能降低了癌细胞的运动性。根据提出的机制(SAFB), SKA1的这些生物活性可能是由其与支架附着因子B的特异性相互作用引起的,这可能进一步抑制双特异性磷酸酶6 (DUSP6)的转录。我们的发现可能为研究SKA1调控的肿瘤转移提供了新的途径,并提示SKA1是肾癌的一个有前景的治疗靶点。
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