Lee Gayoung, Kim Hyun-Man
Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, Program of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
Biochem Biophys Res Commun. 2017 Jun 10;487(4):862-867. doi: 10.1016/j.bbrc.2017.04.142. Epub 2017 Apr 27.
Cell scattering of epithelial carcinoma cancer cells is one of the critical event in tumorigenesis. Cells losing epithelial cohesion detach from aggregated epithelial cell masses and may migrate to fatal organs through metastasis. The present study investigated the molecular mechanism by which squamous cell carcinoma cells grow scattered at the early phase of transformation while maintaining the epithelial phenotype. We studied YD-10B cells, which are established from human oral squamous cell carcinoma, because the cells grow scattered without the development of E-cadherin junctions (ECJs) under routine culture conditions despite the high expression of functional E-cadherin. The functionality of their E-cadherin was demonstrated in that YD-10B cells developed ECJs, transiently or persistently, when they were cultured on substrates coated with a low amount of fibronectin or to confluence. The phosphorylation of JNK was up-regulated in YD-10B cells compared with that in human normal oral keratinocyte cells or human squamous cell carcinoma cells, which grew aggregated along with well-organized ECJs. The suppression of JNK activity induced the aggregated growth of YD-10B cells concomitant with the development of ECJs. These results indicate for the first time that inherently up-regulated JNK activity induces the scattered growth of the oral squamous cell carcinoma cells through down-regulating the development of ECJ despite the expression of functional E-cadherin, a hallmark of the epithelial phenotype.
上皮癌细胞的细胞散射是肿瘤发生中的关键事件之一。失去上皮细胞黏附性的细胞从聚集的上皮细胞团块中脱离，并可能通过转移迁移到致命器官。本研究调查了鳞状细胞癌细胞在转化早期生长分散同时保持上皮表型的分子机制。我们研究了从人口腔鳞状细胞癌建立的YD-10B细胞，因为尽管功能性E-钙黏蛋白高表达，但在常规培养条件下这些细胞生长分散且未形成E-钙黏蛋白连接（ECJ）。当它们在涂有少量纤连蛋白的底物上培养或培养至汇合时，YD-10B细胞会短暂或持续形成ECJ，这证明了其E-钙黏蛋白的功能。与人类正常口腔角质形成细胞或人类鳞状细胞癌细胞相比，YD-10B细胞中JNK的磷酸化上调，后者与组织良好的ECJ一起聚集生长。抑制JNK活性诱导YD-10B细胞聚集生长并伴随ECJ的形成。这些结果首次表明，尽管功能性E-钙黏蛋白表达，而E-钙黏蛋白是上皮表型的标志，但固有上调的JNK活性通过下调ECJ的形成诱导口腔鳞状细胞癌细胞的分散生长。
