Digital Image Analysis-Based Evaluation of Claudin-1 and Claudin-7 Delocalization in Cutaneous Squamous Cell Carcinoma and in Its Precancerous State.
Digital Image Analysis-Based Evaluation of Claudin-1 and Claudin-7 Delocalization in Cutaneous Squamous Cell Carcinoma and in Its Precancerous State.
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DOI：
10.1155/2022/2750193
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发表时间：
2022
影响因子：
--
通讯作者：
Fang, Hong
中科院分区：
文献类型：
--
作者：
Xu, Lina;Pan, Yunlei;Tang, Shunli;Bai, Juan;Wu, Yinhua;Qiao, Jianjun;Fang, Hong
越来越多的证据表明，跨膜蛋白Claudin-1和Claudin-7向细胞质和/或细胞核的离域发生在各种肿瘤中。然而，它们在细胞膜、细胞质和细胞核的亚细胞分布及其与信号通路的关系尚未阐明。我们首先使用ImageJ软件确定这些蛋白质在膜、细胞质和细胞核中的表达，并自动收集异型增生（光化性角化病（AK））、原位癌（CIS; Bowen病（BD））和浸润性皮肤鳞状细胞癌（SCC）的免疫组织化学定量用于数字图像分析（DIA）。检测p-ERK、p-AKT和p-mTOR的活性及其与亚细胞Claudin-1和Claudin-7的相关性。最后，我们验证了Claudin-1和Claudin-7在培养的人正常角质形成细胞和皮肤SCC细胞的细胞质和细胞核中的离域。Claudin-1和Claudin-7在阳光暴露的皮肤、AK、BD和SCC中通过膜、细胞质和细胞核染色显示为离域的。BD细胞膜和细胞质Claudin-1（核Claudin-1减少但无显著性差异）均高于AK，而Claudin-7几乎相反。在鳞状细胞癌中，Claudin-1在胞浆和胞核中的表达（膜Claudin-1表达无显著性差异）低于AK和日光暴露皮肤，而Claudin-7在膜和胞浆中的表达较高，而在胞核中的表达较低。此外，p-AKT和p-mTOR（而不是p-ERK）在SCC中下调。亚细胞Claudin-1和Claudin-7不仅相互相关，而且在BD中与p-ERK相关，在SCC中与p-AKT和p-mTOR相关。总之，这些结果暗示了Claudin-1和Claudin-7的非定位及其与MAPK/ERK和PI 3 K-AKT-mTOR信号通路在皮肤SCC的肿瘤发生和浸润中的相关性。
Accumulating evidence has revealed that delocalization of the transmembrane proteins, Claudin-1 and Claudin-7, to the cytoplasm and/or nucleus occurs in various tumors. However, their subcellular distribution in terms of the membrane, cytoplasm, and nucleus and relationship with signaling pathways have not been elucidated during carcinogenesis. We first determined the expression of these proteins in the membrane, cytoplasm, and nucleus using ImageJ software and automatically collected the immunohistochemical quantification of dysplasia (actinic keratosis (AK)), carcinoma in situ (CIS; Bowen's disease (BD)), and invasive cutaneous squamous cell carcinoma (SCC) for digital image analysis (DIA). The activity of p-ERK, p-AKT, and p-mTOR and their correlation with subcellular Claudin-1 and Claudin-7 were also performed. Finally, we validated Claudin-1 and Claudin-7 delocalization at the cytoplasm and nucleus in cultured human normal keratinocytes and cutaneous SCC cells. Claudin-1 and Claudin-7 were delocalized as revealed by membranous, cytoplasmic, and nuclear staining in sun-exposed skin, AK, BD, and SCC. In BD, both membranous and cytoplasmic Claudin-1 (nuclear Claudin-1 decrease but no significant difference) were higher than AK, while Claudin-7 almost had the opposite situation. In SCC, cytoplasmic and nuclear Claudin-1 (membranous Claudin-1 no significant difference) was lower than in AK and sun-exposed skin, while Claudin-7 had higher membranous and cytoplasmic but lower nuclear expression. Moreover, p-AKT and p-mTOR (but not p-ERK) were downregulated in the SCC. Subcellular Claudin-1 and Claudin-7 were not only correlated with each other, but also correlated with p-ERK in BD and p-AKT and p-mTOR in SCC. Together, these results imply the delocalization of Claudin-1 and Claudin-7 and their correlation with MAPK/ERK and PI3K-AKT-mTOR signaling pathways in tumorigenesis and infiltration in cutaneous SCC.
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DOI：
10.1016/j.bbrc.2017.06.052
发表时间：
2017-08-19
影响因子：
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2000-01-01
期刊：
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影响因子：
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作者：
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影响因子：
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