The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer
The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer
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DOI：
10.1158/0008-5472.can-05-3855
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发表时间：
2006-02-15
期刊：
影响因子：
11.2
通讯作者：
Theodorescu, D
中科院分区：
文献类型：
--
作者：
Smith, SC;Oxford, G;Theodorescu, D
Ral GTP酶是转化、肿瘤发生和癌症进展的重要介质。我们最近通过分析RalA/B缺失的膀胱癌细胞的表达，确定了转移相关蛋白CD 24，一种糖基化磷脂酰肌醇连接的表面蛋白，作为Ral信号传导的下游靶点。由于CD 24在膀胱和许多其他肿瘤类型中高度表达，我们试图确定这种蛋白质是否在维持恶性表型中起重要作用。在这里，我们表明，CD 24功能的损失，来自常见的肿瘤类型的细胞系与细胞增殖率下降，软琼脂中的克隆形成，肌动蛋白细胞骨架的变化，诱导细胞凋亡。鉴于这些表型，我们通过免疫组织化学对CD 24进行了评估，以确定CD 24是否是预后癌症生物标志物。多变量分析显示，CD 24表达增加与患者无病生存期缩短相关（P = 0.07）。总之，我们表明，CD 24是一种新的和功能相关的雷尔调节的目标和一个潜在的重要的预后标志物。我们认为，这些见解可能会导致未来的治疗方法，寻求消除癌细胞中的CD 24功能。
Ral GTPases are important mediators of transformation, tumorigenesis, and cancer progression. We recently identified the metastasis-associated protein CD24, a glycosyl phospliatidyl inositol-linked surface protein, as a downstream target of Ral signaling by profiling the expression of RalA/B-depleted bladder carcinoma cells. Because CD24 is highly expressed in bladder and many other tumor types, we sought to determine if this protein plays an essential role in maintaining the malignant phenotype. Here, we show that loss of CD24 function in cell lines derived from common tumor types is associated with decreased rates of cell proliferation, clonogenicity in soft agar, changes in the actin cytoskeleton, and induction of apoptosis. Given these phenotypes, we evaluated a human bladder cancer tissue microarray by immunohistochemistry for CD24 to determine if CD24 is a prognostic cancer biomarker. Multivariate analysis showed that increased CD24 expression correlated with shorter patient disease-free survival (P = 0.07). In conclusion, we show that CD24 is a novel and functionally relevant Ral-regulated target and a potentially important prognostic marker. We suggest that these insights may lead to future therapeutic approaches that seek to eliminate CD24 function in cancer cells.