Necroptosis in head and neck squamous cell carcinoma: characterization of clinicopathological relevance and in vitro cell model
Necroptosis in head and neck squamous cell carcinoma: characterization of clinicopathological relevance and in vitro cell model
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头颈鳞状细胞癌坏死性凋亡：临床病理相关性和体外细胞模型的表征
DOI：
10.1038/s41419-020-2538-5
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发表时间：
2020-05-22
影响因子：
9
通讯作者：
Liang, Yujie
中科院分区：
文献类型：
--
作者：
Li, Jingyuan;Huang, Sihui;Liang, Yujie
坏死性凋亡是最近发现的具有坏死样形态的程序性细胞死亡（PCD）形式。然而，它的存在和潜在的影响，就头部和颈部鳞状细胞癌（HNSCC）仍然是未知的。本研究的目的是揭示HNSCC中坏死性凋亡的状态及其临床病理学意义，并建立体外模型。我们首先分析了HNSCC患者组织中p-MLKL、MLKL和肿瘤坏死的水平以及它们与临床病理特征的相关性。结果表明，大约一半的肿瘤坏死可归因于坏死性凋亡，坏死性凋亡的程度是患者总生存期和无进展生存期的独立预后指标。在此基础上，我们建立了TNF-α、Smac模拟物和zVAD-β（TSZ）联合作用于两种HNSCC细胞株的体外坏死性凋亡模型，并进行了全面验证。最后，我们采用该模型，并证明坏死性凋亡可以通过释放损伤相关分子模式促进HNSCC细胞的迁移和侵袭。总之，我们的研究首次揭示了HNSCC中的坏死性凋亡状态，并提供了两种HNSCC细胞系中坏死性凋亡的新体外模型。此外，我们的研究结果表明，坏死性凋亡可能是一个潜在的癌症促进剂在HNSCC。本研究为进一步研究HNSCC的坏死性凋亡奠定了基础。
Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient’s overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns. In conclusion, our study unveiled the necroptotic status in HNSCC for the first time and provided a novel in vitro model of necroptosis in two HNSCC cell lines. In addition, our results indicated that necroptosis may be a potential cancer promoter in HNSCC. This study may serve as the foundation for future researches of necroptosis in HNSCC.