STAT3 mediates resistance to anoikis and promotes invasiveness of nasopharyngeal cancer cells
STAT3 mediates resistance to anoikis and promotes invasiveness of nasopharyngeal cancer cells
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DOI：
10.3892/ijmm.2017.3151
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发表时间：
2017-11-01
影响因子：
5.4
通讯作者：
Chen, Yan-Jang
中科院分区：
文献类型：
--
作者：
Lin, Chien-Hung;Chiang, Ming-Chang;Chen, Yan-Jang
鼻咽癌（NPC）是一种起源于鼻咽上皮细胞的肿瘤，是东南亚和台湾的地方病。局部复发转移的鼻咽癌患者预后差。对失巢凋亡的抵抗是转移的肿瘤细胞的主要特征。然而，NPC细胞抵抗失巢凋亡并能够转移的机制尚未完全阐明。在本研究中，获得失巢凋亡的阻力进行了分析，在TW 01和TW 06人鼻咽癌细胞系生长在锚定非依赖性条件下。TW 01和TW 06细胞对失巢凋亡有较强的抵抗能力，并具有较高的迁移和侵袭能力。与贴壁细胞相比，这些抗失巢凋亡的NPC细胞表现出显著增加的信号转导和转录激活因子3（Stat 3）的表达。此外，STAT 3抑制剂阻断STAT 3表达或STAT 3沉默显著增加了失巢凋亡抗性NPC细胞中的失巢凋亡。此外，沉默STAT 3不仅降低了NPC细胞抵抗失巢凋亡的能力，而且还逆转了它们的侵袭性。上皮-间质转化相关蛋白和CD 44的表达在STAT 3敲低后也显著降低。本研究的结果证实，STAT 3介导失巢凋亡抗性，增强NPC细胞的细胞迁移和侵袭，并且STAT 3的活化可以增加转移能力，表明STAT 3在赋予失巢凋亡抗性和增强NPC细胞的侵袭特性中的关键作用。
Nasopharyngeal carcinoma (NPC), a tumor arising from the epithelial cells of the nasopharynx, is endemic in Southeast Asia and Taiwan. The prognosis of NPC patients with local recurrence and metastasis is poor. Resistance to anoikis is a primary characteristic of tumor cells that metastasize. However, the mechanism through which NPC cells resist anoikis and are able to metastasize has not been fully elucidated. In the present study, the acquisition of anoikis resistance was analyzed in the TW01 and TW06 human NPC cell lines growing under anchorage-independent conditions. A considerable number of TW01 and TW06 cells was found to be resistant to anoikis and exhibited a higher capability of migration and invasion. These anoikis-resistant NPC cells exhibited significantly increased expression of signal transducer and activation of transcription 3 (Stat 3) compared with adherent cells. Furthermore, blockade of STAT3 expression by STAT3 inhibitors or STAT3 silencing significant increased anoikis in anoikis-resistant NPC cells. Moreover, silencing STAT3 not only reduced the capacity of NPC cells to resist anoikis, but also reversed their invasive properties. The expression of epithelial-to-mesenchymal transition-related proteins and CD44 was also significantly decreased following STAT3 knockdown. The results of the present study established that STAT3 mediates anoikis resistance, with enhanced cell migration and invasion of NPC cells, and that activation of STAT3 may increase metastatic capacity, indicating the crucial role of STAT3 in conferring anoikis resistance and enhanced invasive properties to NPC cells.