DEC1 在 OSF 上皮细胞中的过表达通过激活 FAK/Akt 信号轴促进间充质转化。

Overexpression of DEC1 in the epithelium of OSF promotes mesenchymal transition via activating FAK/Akt signal axis.

机构信息

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Oral Pathol Med. 2022 Oct;51(9):780-790. doi: 10.1111/jop.13350. Epub 2022 Sep 19.

DOI:10.1111/jop.13350

PMID:36053880

Abstract

BACKGROUND

Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium.

METHODS

Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings.

RESULTS

DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt.

CONCLUSION

In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.

摘要

背景

先前关于口腔黏膜下纤维性变（OSF）的研究大多集中在成纤维细胞的激活和胶原代谢上，而对上皮组织涉及较少。由于我们已经报道了分化胚胎软骨细胞表达基因 1（DEC1）在口腔癌和其他癌前病变中的作用，本研究旨在探讨其在 OSF 上皮组织中的作用。

方法

利用包含 33 例 OSF 和 14 例正常口腔黏膜（NOM）组织的组织芯片，研究 DEC1 和其他蛋白的表达情况。用槟榔碱和/或缺氧处理人口腔角质形成细胞，模拟 OSF 上皮组织，并检测其形态和蛋白变化。抑制 DEC1 用于探讨其介导作用。最后，通过局部注射槟榔碱在颊黏膜构建 OSF 动物模型来验证我们的发现。

结果

与 NOM 相比，OSF 上皮组织中可检测到 DEC1 的过表达，随后是磷酸化 FAK 和 Akt，且 DEC1 与它们呈显著正相关。细胞学实验表明，类似 OSF 的处理可上调 DEC1 的表达，随后抑制 E-钙黏蛋白，但抑制磷酸化 FAK、Akt，而 DEC1 的敲低则可抑制这些作用。此外，OSF 小鼠的颊黏膜上皮组织中 DEC1 的表达较高，同时磷酸化 FAK 和 Akt 也发生了同步改变。