Transforming growth factor β1 enhances sternness of head and neck squamous cell carcinoma cells through activation of Wnt signaling
Transforming growth factor β1 enhances sternness of head and neck squamous cell carcinoma cells through activation of Wnt signaling
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DOI：
10.3892/ol.2016.5336
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发表时间：
2016-12-01
期刊：
影响因子：
2.9
通讯作者：
Lim, Young-Chang
中科院分区：
文献类型：
--
作者：
Bae, Woo-Jin;Lee, Sang-Hyuk;Lim, Young-Chang
转化生长因子β (TGF β)配体，包括TGF β 1，是一种多功能细胞因子，是细胞生长、分化和炎症的关键调节因子。TGF - β信号失调在包括头颈部鳞状细胞癌（HNSCC）在内的许多实体肿瘤中都很常见。此前，TGF β配体也被报道与胶质瘤干细胞样细胞的严重度增强有关。然而，它们在HNSCC癌症干细胞（CSCs）中的作用尚未被探索。本研究证实TGF β 1可丰富HNSCC csc的特性。TGF β 1促进原发性HNSCC CSCs的球体形成，并增加严重度相关基因（Oct4和Sox2）的表达。此外，用TGF β 1外源性处理细胞后，醛脱氢酶（ALDH）阳性细胞的数量增加。此外，TGF β 1刺激后，细胞对顺铂的抗性增强，Twist、Snail和Slug的表达升高。从机制上讲，TGF β 1是Wnt/ β -catenin信号传导的上游刺激物。总的来说，本研究结果为开发TGF β 1信号抑制策略治疗HNSCC csc提供了见解。
Transforming growth factor beta (TGF beta) ligands, including TGF beta 1, are multifunctional cytokines known as key regulators of cell growth, differentiation and inflammation. Dysregulated TGF beta signaling is common in numerous solid tumors, including head and neck squamous cell carcinoma (HNSCC). Previously, TGF beta ligands were also reported to be associated with an enhancement of sternness in glioma stem-like cells. However, their role in HNSCC cancer stem cells (CSCs) has not been explored. The present study demonstrated that TGF beta 1 enriches the properties of HNSCC CSCs. TGF beta 1 promoted sphere formation and increased sternness-associated gene expression (Oct4 and Sox2) of primary HNSCC CSCs. Additionally, the population of aldehyde dehydrogenase (ALDH)-positive cells was increased subsequent to exogenous treatment of cells with TGF beta 1. In addition, following stimulation with TGF beta 1, the cells exhibited more resistance to cisplatin and elevated expression of Twist, Snail and Slug. Mechanistically, TGF beta 1 acts as an upstream stimulator of Wnt/beta-catenin signaling. Collectively, the present findings provide insights toward the development of TGF beta 1 signaling inhibition strategies for treating HNSCC CSCs.