Cell polarity protein CRB3 is an independent favorable prognostic factor for clear cell renal cell carcinoma

Cell polarity protein CRB3 is an independent favorable prognostic factor for clear cell renal cell carcinoma
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细胞极性蛋白CRB3是透明细胞肾细胞癌的独立有利预后因素

DOI:
10.3892/ijo.2014.2763
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发表时间:
2015-02-01
影响因子:
5.2
通讯作者:
Liu, Peijun
Liu, Peijun
中科院分区:
医学2区
文献类型:
--
作者:
Mao, Xiaona;Li, Pingping;Liu, Peijun

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上皮细胞具有顶部-基底极性,上皮细胞极性的丧失有助于肿瘤发生和癌症进展。Crumbs(CRB)极性蛋白在上皮极性维持、顶端膜形成和组织形态发生中起着至关重要的作用。尽管越来越多的证据表明去调节的极性蛋白参与癌症,但目前对CRB(果蝇)的作用,特别是CRB的同源物CRB 3在透明细胞肾细胞癌(ccRCC)中的作用知之甚少。研究表明CRB 3在非人哺乳动物细胞中可能作为肿瘤抑制因子发挥作用;本研究旨在检测CRB 3在ccRCC中的表达状况以及CRB 3表达与ccRCC患者临床病理参数之间的关系。我们的结果显示CRB 3在ccRCC组织中弱表达,但在邻近的正常肾组织中强表达。CRB 3表达缺失的患者的总生存期(OS)显著短于CRB 3表达阳性的患者。我们的研究结果表明CRB 3可能是ccRCC患者的独立有利预后因素。我们还发现CRB 3过表达抑制786-0细胞的侵袭和迁移,CRB 3表达缺失促进人胚肾293 T(HEK 293 T)细胞的侵袭和迁移。这一发现可能解释了为什么CRB 3阴性表达与人类ccRCC的不良预后相关。总而言之,我们的数据表明CRB 3可用作人类ccRCC的新的独立有利预后因素。
Epithelial cells possess apical-basal polarity and loss of epithelial cell polarity contributes to tumorigenesis and cancer progression. The Crumbs (CRB) polarity protein plays a crucial role in epithelial polarity maintenance, apical membrane formation, and tissue morphogenesis. Although evidence is increasing on involvement of deregulated polarity proteins in cancers, little is currently known about the roles of the CRB (Drosophila), especially the roles of CRB3, a homolog of the CRB, in clear cell renal cell carcinoma (ccRCC). Studies have shown that CRB3 may act as a tumor suppressor in non-human mammalian cells; the study here was aimed to examine the expression status of CRB3 in ccRCC and the relationships between CRB3 expression and clinicopathologic parameters of ccRCC patients. Our results showed that CRB3 was weakly expressed in ccRCC tissues, but strongly expressed in adjacent normal kidney tissues. Patients with loss of CRB3 expression showed a significantly shorter overall survival (OS) than patients with positive CRB3 expression. Our results suggested that CRB3 may be an independent favorable prognostic factor for patients with ccRCC. We also found that overexpression of CRB3 restrained invasion and migration of 786-0 cells and loss of CRB3 expression promoted invasion and migration of human embryonic kidney 293T (HEK 293T) cells. This finding may explain why the negative CRB3 expression was associated with poor prognosis in human ccRCC. Altogether, our data demonstrated that CRB3 may be used as a new independent favorable prognostic factor for human ccRCC.