Naa10p 与 IKKα 的相互作用通过 TGF-β1/Smad 通路调节口腔鳞状细胞癌中的 EMT。
Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-β1/Smad pathway.
机构信息
Key Laboratory of Xinjiang Endemic and Ethnic Disease, School of Medicine, Shihezi University, Shihezi, China.
Department of Stomatology, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China.
出版信息
J Cell Mol Med. 2021 Jul;25(14):6760-6772. doi: 10.1111/jcmm.16680. Epub 2021 May 31.
Epithelial-mesenchymal transition (EMT) has been contributed to increase migration and invasion of cancer cells. However, the correlate of Naa10p and IKKα with EMT in oral squamous cell carcinoma (OSCC) is not yet fully understood. In our present study, we found N-α-acetyltransferase 10 protein (Naa10p) and IκB kinase α (IKKα) were abnormally abundant in oral squamous cell carcinoma (OSCC). Bioinformatic results indicate that the expression of Naa10p and IKKα is correlated with TGF-β1/Smad and EMT-related molecules. The Transwell migration, invasion, qRT-PCR and Western blot assay indicated that Naa10p repressed OSCC cell migration, invasion and EMT, whereas IKKα promoted TGF-β1-mediated OSCC cell migration, invasion and EMT. Mechanistically, Naa10p inhibited IKKα activation of Smad3 through the interaction with IKKα directly in OSCC cells after TGF-β1 stimulation. Notably, knockdown of Naa10p reversed the IKKα-induced change in the migration, invasion and EMT-related molecules in OSCC cells after TGF-β1 stimulation. These findings suggest that Naa10p interacted with IKKα mediates EMT in OSCC cells through TGF-β1/Smad, a novel pathway for preventing OSCC.
上皮-间充质转化（EMT）被认为增加了癌细胞的迁移和侵袭。然而，Naa10p 和 IKKα 与口腔鳞状细胞癌（OSCC）中的 EMT 的相关性尚不完全清楚。在本研究中，我们发现 N-α-乙酰转移酶 10 蛋白（Naa10p）和 IκB 激酶α（IKKα）在口腔鳞状细胞癌（OSCC）中异常丰富。生物信息学结果表明，Naa10p 和 IKKα 的表达与 TGF-β1/Smad 和 EMT 相关分子相关。Transwell 迁移、侵袭、qRT-PCR 和 Western blot 分析表明，Naa10p 抑制 OSCC 细胞迁移、侵袭和 EMT，而 IKKα 促进 TGF-β1 介导的 OSCC 细胞迁移、侵袭和 EMT。在机制上，Naa10p 在 TGF-β1 刺激后通过与 IKKα 直接相互作用抑制 IKKα 对 Smad3 的激活。值得注意的是，敲低 Naa10p 逆转了 TGF-β1 刺激后 IKKα 诱导的 OSCC 细胞迁移、侵袭和 EMT 相关分子的变化。这些发现表明，Naa10p 通过 TGF-β1/Smad 与 IKKα 相互作用，在 OSCC 细胞中介导 EMT，这是一种预防 OSCC 的新途径。
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