STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling.
STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling.
复制标题
STC2通过调节PI3K/AKT/Snail信号促进头颈部鳞状细胞癌转移
DOI：
10.18632/oncotarget.13355
复制
发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Yang S;Ji Q;Chang B;Wang Y;Zhu Y;Li D;Huang C;Wang Y;Sun G;Zhang L;Guan Q;Xiang J;Wei W;Lu Z;Liao T;Meng J;Wang Z;Ma B;Zhou L;Wang Y;Yang G
哺乳动物肽激素斯坦钙素2 （STC2）在许多人类癌症中起致癌作用。然而，STC2在人头颈部鳞状细胞癌（HNSCC）中的确切功能尚不清楚。我们旨在探讨STC2在HNSCC中的功能和临床意义。通过体外和体内实验，我们发现STC2过表达可抑制细胞凋亡，促进细胞增殖、迁移、侵袭，并在G1/S过渡阶段阻滞细胞周期。相比之下，STC2的沉默抑制了这些活性。我们进一步发现，STC2通过蜗牛介导的vimentin升高和E-cadherin降低，上调AKT磷酸化，促进HNSCC转移。这些反应通过沉默STC2/Snail表达或抑制pAKT活性而被阻断。此外，临床数据表明，在伴有区域淋巴结转移的HNSCC患者的肿瘤样本中，STC2的高表达与pAKT和Snail的高水平相关（P < 0.01）。因此，我们得出结论，STC2通过PI3K/AKT/Snail信号轴控制HNSCC转移，针对STC2的靶向治疗可能是有效治疗转移性HNSCC患者的新策略。
The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in many human cancers. However, the exact function of STC2 in human head and neck squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we show that overexpression of STC2 suppressed cell apoptosis, promoted cell proliferation, migration, invasion, and cell cycle arrest at the G1/S transition. By contrast, silencing of STC2 inhibited these activities. We further show that STC2 upregulated the phosphorylation of AKT and enhanced HNSCC metastasis via Snail-mediated increase of vimentin and decrease of E-cadherin. These responses were blocked by silencing of STC2/Snail expression or inhibition of pAKT activity. Furthermore, clinical data indicate that high STC2 expression was associated with high levels of pAKT and Snail in tumor samples from HNSCC patients with regional lymph node metastasis (P < 0.01). Thus, we conclude that STC2 controls HNSCC metastasis via the PI3K/AKT/Snail signaling axis and that targeted therapy against STC2 may be a novel strategy to effectively treat patients with metastatic HNSCC.