Snail-induced EMT promotes cancer stem cell-like properties in head and neck cancer cells

Snail-induced EMT promotes cancer stem cell-like properties in head and neck cancer cells
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DOI:
10.3892/or.2015.4348
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发表时间:
2016-01-01
期刊:
影响因子:
4.2
通讯作者:
Kitahara, Tadashi
Kitahara, Tadashi
中科院分区:
医学3区
文献类型:
--
作者:
Ota, Ichiro;Masui, Takashi;Kitahara, Tadashi

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上皮间质转化(EMT)是癌细胞侵袭和转移的关键过程。此外,EMT 可以在多种肿瘤类型中诱导癌症干细胞 (CSC) 样表型。我们证明,Snail 是促进 EMT 并介导多种类型恶性肿瘤(包括头颈鳞状细胞癌 (HNSCC))中癌细胞迁移和侵袭的主要调节因子之一。在本研究中,我们研究了 Snail 在 HNSCC 中通过 EMT 诱导和维持 CSC 样特性的作用。我们建立了用 Snail 转染的 HNSCC 细胞系。通过实时 RT-PCR 和蛋白质印迹分析评估干细胞标记物。使用球体形成和 WST-8 测定以及化学敏感性和鸡绒毛尿囊膜体内侵袭测定来评估 CSC 特性。引入 Snail 在 HNSCC 细胞中诱导 EMT 特性。此外,Snail诱导的EMT保持了CSC样表型,并增强了球体形成能力、化疗耐药性和侵袭能力。这些数据表明,Snail 可能是制定 HNSCC 治疗策略的关键分子靶点之一。
Epithelial-mesenchymal transition (EMT) is a key process involved in the invasion and metastasis of cancer cells. Furthermore, EMT can induce a cancer stem cell (CSC)-like phenotype in a number of tumor types. We demonstrated that Snail is one of the master regulators that promotes EMT and mediates cancer cell migration and invasion in many types of malignancies including head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the role of Snail in inducing and maintaining CSC-like properties through EMT in HNSCC. We established HNSCC cell lines transfected with Snail. Stem cell markers were evaluated with real-time RT-PCR and western blot analysis. CSC properties were assessed using sphere formation and WST-8 assays as well as chemosensitivity and chick chorioallantoic membrane in vivo invasion assays. Introduction of Snail induced EMT properties in HNSCC cells. Moreover, Snail-induced EMT maintained the CSC-like phenotype, and enhanced sphere formation capability, chemoresistance and invasive ability. These data suggest that Snail could be one of the critical molecular targets for the development of therapeutic strategies for HNSCC.