Akiyama Naotaro, Yamamoto-Fukuda Tomomi, Kojima Hiromi
Department of Otorhinolaryngology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.
Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
J Int Adv Otol. 2025 Jan 27;21(1):1-8. doi: 10.5152/iao.2025.241652.
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.
外耳道鳞状细胞癌(EAC)是一种罕见癌症,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。机械转导以Yes相关蛋白(YAP)信号传导而闻名。当YAP易位至细胞核时,L1细胞粘附分子(L1CAM)作为机械转导的效应器被激活。岩藻糖基转移酶8(FUT8)对L1CAM的核心岩藻糖基化与肿瘤恶性程度有关,可调节L1CAM细胞外结构域的裂解。方法:在本研究中,通过体外拉伸试验对YAP、L1CAM和FUT8进行表达分析。还对人EACSCC和正常皮肤标本进行了免疫组织化学检测。结果:在拉伸应力下,人鳞状细胞癌细胞系(HSC1)中FUT8阳性细胞的标记指数显示YAP核转位显著高于人角质形成细胞系。拉伸应力显著增加了HSC1细胞中全长L1CAM的表达水平。此外,在晚期人EACSCC组织中通过免疫组织化学证实了FUT8和L1CAM的共定位。结论:这些结果表明,在机械转导作用下L1CAM表达增加,并且可能通过FUT8调节避免L1CAM的裂解。