Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. A loss-of-function strategy using shRNA targeting STC2 was employed to investigate STC2 in vitro effects on proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) and possible activation of signaling pathways. Moreover, STC2 effects were assessed in vivo in a xenograft mouse cancer model. High expression of STC2 was significantly associated with poor disease-specific survival (HR: 2.67, 95% CI: 1.37-5.21, p = 0.001) and high rate of recurrence with a hazard ratio of 2.80 (95% CI: 1.07-5.71, p = 0.03). In vitro downregulation of STC2 expression in OSCC cells attenuated proliferation, migration and invasiveness while increased apoptotic rates. In addition, the STC2 downregulation controlled EMT phenotype of OSCC cells, with regulation on E-cadherin, vimentin, Snail1, Twist and Zeb2. The reactivation of STC2 was observed in the STC2 knockdown cells in the in vivo xenograft model, and no influence on tumor growth was observed. Modulation of STC2 expression levels did not alter consistently the phosphorylation status of CREB, ERK, JNK, p38, p70 S6K, STAT3, STAT5A/B and AKT. Our findings suggest that STC2 overexpression is an independent marker of OSCC outcome and may contribute to tumor progression via regulation of proliferation, survival and invasiveness of OSCC cells.

中文翻译：

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斯坦钙蛋白2有助于侵略性，是口腔鳞状细胞癌的预后指标。

矿物质代谢过程中调节钙和磷酸盐稳态的糖蛋白斯坦钙蛋白2（STC2）在肿瘤发生和癌症进展中似乎显示出多种作用。本研究旨在探讨STC2在口腔鳞状细胞癌（OSCC）中的预后价值及其在口腔肿瘤发生中的意义。通过免疫组织化学在2个独立的OSCC组织队列中检查了STC2的表达。利用靶向STC2的shRNA的功能丧失策略来研究STC2在体外对增殖，凋亡，迁移，侵袭，上皮-间质转化（EMT）和信号通路可能激活的影响。而且，在异种移植小鼠癌症模型中体内评估了STC2作用。STC2的高表达与疾病特异性生存率差显着相关（HR：2.67，95％CI：1。37-5.21，p = 0.001）和较高的复发率，危险比为2.80（95％CI：1.07-5.71，p = 0.03）。体外下调OSCC细胞中STC2的表达可减缓增殖，迁移和侵袭性，同时提高细胞凋亡率。此外，STC2下调控制了OSCC细胞的EMT表型，并调控了E-钙粘蛋白，波形蛋白，Snail1，Twist和Zeb2。在体内异种移植模型中的STC2敲低细胞中观察到STC2的重新激活，未观察到对肿瘤生长的影响。STC2表达水平的调节并没有一致地改变CREB，ERK，JNK，p38，p70 S6K，STAT3，STAT5A / B和AKT的磷酸化状态。我们的发现表明，STC2的过表达是OSCC结果的独立标志，可能通过调节增殖来促进肿瘤进展，