牵拉后细胞及人EACSCC组织中L1细胞粘附分子及聚焦转移酶8的表达分析。

Naotaro Akiyama, Tomomi Yamamoto-Fukuda, Hiromi Kojima
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引用次数: 0

摘要

背景:外耳道(EAC)鳞状细胞癌(SCC)是一种罕见的癌症,晚期预后较差。机械应力与外耳道鳞状细胞癌(EACSCC)有关,但分子机制尚未阐明。机械转导是众所周知的yes相关蛋白(YAP)信号传导。当YAP转运到细胞核时,L1细胞粘附分子(L1CAM)作为机械转导的效应器被激活。聚焦转移酶8 (FUT8)对L1CAM的核心聚焦化与肿瘤恶性程度有关,调节L1CAM细胞外结构域的切割。方法:采用拉伸法对YAP、L1CAM、FUT8进行体外表达分析。对人EACSCC和正常皮肤标本进行免疫组化。结果:拉伸应激下,人SCC细胞系(HSC1)中fut8阳性细胞表现出YAP核易位的标记指数明显高于人角质形成细胞系。拉伸应激显著提高HSC1细胞全长L1CAM的表达水平。此外,在晚期人EACSCC组织中,免疫组织化学证实了FUT8和L1CAM的共定位。结论:这些结果提示在机械转导下L1CAM的表达增加,可能通过FUT8调节避免了L1CAM的裂解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of L1 Cell Adhesion Molecule and Fucosyltransferase 8 Expression in Cells After Stretch and Human EACSCC Tissue.

Background: External auditory canal (EAC) squamous cell carcinoma (SCC) is classified as a rare cancer and has a poor prognosis at advanced stages. Mechanical stress has been implicated in external auditory canal squamous cell carcinoma (EACSCC), but the molecular mechanism has not been elucidated. Mechanotransduction is well-known for Yes-associated protein (YAP) signaling. When YAP is translocated to the nucleus, the L1 cell adhesion molecule (L1CAM) is activated as an effector of mechanotransduction. Core fucosylation of L1CAM by Fucosyltransferase 8 (FUT8) has been implicated in the degree of tumor malignancy, modulating cleavage of the extracellular domain of L1CAM. Methods: In this study, an expression analysis of YAP, L1CAM, and FUT8 was performed by stretch assay in vitro. Immunohistochemistry was also performed in human EACSCC and normal skin specimens. Results: The labeling index of FUT8-positive cells exhibited YAP nuclear translocation under stretch stress was significantly higher in a human SCC cell line (HSC1) than in a human keratinocyte cell line. Stretch stress significantly increased the expression levels of full-length L1CAM in HSC1 cells. Moreover, colocalization of FUT8 and L1CAM was demonstrated immunohistochemically in advanced human EACSCC tissues. Conclusion: These results suggested that L1CAM expression is increased under mechanotransduction and may possibly avoid L1CAM cleavage by FUT8 modulation.

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