Stanniocalcin 2 (STC2) expression promotes post-radiation survival, migration and invasion of nasopharyngeal carcinoma cells
Stanniocalcin 2 (STC2) expression promotes post-radiation survival, migration and invasion of nasopharyngeal carcinoma cells
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DOI：
10.2147/cmar.s197607
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Lin, Shaojun
中科院分区：
文献类型：
--
作者：
He, Huocong;Qie, Shuo;Lin, Shaojun
背景：斯钙素2（Stanniocalcin 2，STC 2）在缺氧、营养饥饿和辐射等多种应激条件下表达上调。STC 2的过表达与肿瘤进展和预后不良相关。目的：我们以前证明，STC 2在鼻咽癌（NPC）中的过表达与放射抵抗和肿瘤转移呈正相关，这是改善NPC管理的两个主要临床障碍。然而，它仍然难以捉摸是否STC 2的表达是一个关键的因素，辐射后的生存和转移的NPC celles.Materials和方法：使用耐辐射CNE 2细胞系作为一个模型，我们研究了STC 2的表达的重要性，辐射后的生存，迁移和侵袭。结果：与亲本细胞相比，STC 2-KO细胞在正常培养条件下的增殖能力和形态学特征相似，STC 2基因的缺失并不影响细胞在裸鼠体内的致瘤性。然而，STC 2-KO株系在常氧或低氧条件下表现出对X-辐射的敏感性增加。特别是，在X射线照射下，亲本CNE 2细胞仅轻微地降低而STC 2-KO细胞显著地降低了迁移和侵袭能力。细胞周期分析显示，STC 2的缺失使鼻咽癌细胞聚集于G（1）和G（2）/M期，而S期细胞减少。结论：STC 2的表达可被代谢或治疗应激刺激，是促进鼻咽癌细胞生存和转移的重要因素之一。因此，针对STC 2或相关下游通路可能为克服NPC的放射抵抗和转移提供新的策略。
Background: Stanniocalcin 2 (STC2) expression is upregulated under multiple stress conditions including hypoxia, nutrient starvation and radiation. Overexpression of STC2 correlates with tumor progression and poor prognosis.Purpose: We previously demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and tumor metastasis, two major clinical obstacles to the improvement of NPC management. However, it remains elusive whether STC2 expression is a critical contributing factor for post-radiation survival and metastasis of NPC cells.Materials and methods: Using the radiation resistant CNE2 cell line as a model, we examined the importance of STC2 expression for post-radiation survival, migration and invasion. Here, we report the establishment of STC2 knockout lines (CNE2-STC2-KO) using the CRISPR/Cas9-based genome editing technique.Results: Compared with the parental line, STC2-KO cells showed similar proliferation and morphology in normal culture conditions, and loss of STC2 did not compromise the cell tumorigenicity in nude mice model. However, STC2-KO lines demonstrated increased sensitivity to X-radiation under either normoxic or hypoxic conditions. Particularly, upon X-radiation, parental CNE2 cells only slightly whereas STC2-KO cells remarkably decreased the migration and invasion ability. Cell cycle analysis revealed that loss of STC2 accumulated cells in G(1) and G(2)/M phases but decreased S-population.Conclusion: These data indicate that the expression of STC2, which can be stimulated by metabolic or therapeutic stresses, is one important factor to promote survival and metastasis of post-radiation NPC cells. Therefore, targeting STC2 or relative downstream pathways may provide novel strategies to overcome radiation resistance and metastasis of NPC.