Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis
Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis
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丝甘氨酸是鼻咽癌促进转移的治疗诊断靶点
DOI：
10.1158/0008-5472.can-10-3557
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发表时间：
2011-04-15
期刊：
影响因子：
11.2
通讯作者：
Qian, Chao-Nan
中科院分区：
文献类型：
--
作者：
Li, Xin-Jian;Ong, Choon Kiat;Qian, Chao-Nan
鼻咽癌（NPC）以其高转移潜力而闻名。在这里，我们报告的蛋白聚糖sergylycin作为一个功能上重要的调节转移在这种情况下的鉴定。比较基因组表达谱的NPC细胞系克隆与高，低转移潜力揭示serglycin基因（SRGN）作为一个最上调的基因在高转移性细胞。RNAi介导的sergylycin表达抑制阻断了sergylycin分泌和高转移性细胞的侵袭运动，降低了体内转移能力。相反，在转移性差的细胞中sergylcin过表达增加了它们的运动行为和体内转移能力。生长速率不受sergylycin在高或低转移性细胞。分泌，但不是细菌重组sergylocin促进运动行为，表明糖基化sergylocin活性的关键作用。丝甘肽抑制与波形蛋白的表达减少有关，但与其他上皮-间充质转化蛋白无关。在临床标本中，sergylocin的表达在NPC肝转移瘤中相对于原发性NPC肿瘤显著升高。我们通过对263例鼻咽癌患者的组织芯片进行免疫组化染色，然后进行多因素分析，评估sergylycin的预后价值。原发性NPC中sergylycin的高表达被认为是无远处转移和无病生存的不利的独立指标。我们的研究结果表明，糖基化sergylocin通过自分泌和旁分泌途径调节NPC转移，并且它可以作为NPC患者无转移生存和无病生存的独立预后指标。Cancer Res; 71（8）; 3162-72. (C)2011年AACR。
Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high-and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients. Cancer Res; 71(8); 3162-72. (C) 2011 AACR.