Melanoma progression is associated with the epithelial-mesenchymal transition (EMT) when tumor cells reduce E-cadherin and increase N-cadherin expression resulting in an escape from the microenvironment via loss of cellular adhesion and gain of motility. Transcription factor proteins Snail and ZEB trigger EMT by repression of epithelial markers and activation of mesenchymal properties. This study evaluated E-cadherin, N-cadherin, Snail, ZEB1 and ZEB2 expression by IHC and investigated their relationship with morphological characteristics in cutaneous and oral canine melanoma. Results from melanoma cases demonstrated E-cadherin expression in 45% (9/20) of oral and 58% (22/38) of cutaneous tumors, while N-cadherin expression was observed in 95% (18/19) of oral and 92% (34/37) of cutaneous melanoma. Cytoplasmic and nuclear N-cadherin expression was positively correlated with ZEB1 expression, while the cell membrane N-cadherin expression was positively correlated with ZEB2. In addition, an increase in nuclear N-cadherin expression was associated with reduced Snail expression in cutaneous melanoma and an increase in Snail expression in oral melanoma, indicating that the correlation between N-cadherin and Snail expression is coincident with tumor location. Our data suggest that ZEB family protein is associated with N-cadherin translocation from cell membrane to the cytoplasm and nuclei, and may act as important transcription factors of EMT regulation in canine melanoma.

中文翻译：

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ZEB和Snail表达表明犬黑色素瘤中上皮-间质转化。

当肿瘤细胞减少E-钙黏着蛋白并增加N-钙黏着蛋白表达时，黑素瘤的进展与上皮-间充质转变（EMT）相关，从而通过失去细胞粘附力和获得运动性而逃离微环境。转录因子蛋白Snail和ZEB通过抑制上皮标记和激活间充质来触发EMT。这项研究通过IHC评估了E-cadherin，N-cadherin，Snail，ZEB1和ZEB2的表达，并研究了它们与皮肤和口腔犬黑色素瘤的形态特征之间的关系。黑色素瘤病例的结果表明，E-钙粘蛋白的表达在45％（9/20）的口腔和58％（22/38）的皮肤肿瘤中，而N-钙粘蛋白的表达在95％（18/19）的口腔和92％的皮肤肿瘤中％（34/37）的皮肤黑色素瘤。细胞质和核N-钙粘蛋白的表达与ZEB1表达正相关，而细胞膜N-钙粘蛋白的表达与ZEB2正相关。此外，核N-钙黏着蛋白表达的增加与皮肤黑色素瘤中Snail表达的减少和口腔黑素瘤中Snail表达的增加有关，这表明N-钙黏着蛋白与Snail表达之间的相关性与肿瘤的位置一致。我们的数据表明，ZEB家族蛋白与N-钙粘蛋白从细胞膜到细胞质和细胞核的转运有关，并且可能是犬黑色素瘤EMT调控的重要转录因子。核黑色素钙粘蛋白表达的增加与皮肤黑色素瘤中Snail表达的减少和口腔黑色素瘤中Snail表达的增加有关，表明N-钙黏着蛋白与Snail表达之间的相关性与肿瘤的位置一致。我们的数据表明，ZEB家族蛋白与N-钙粘蛋白从细胞膜到细胞质和细胞核的转运有关，并且可能是犬黑色素瘤EMT调控的重要转录因子。核黑色素钙粘蛋白表达的增加与皮肤黑色素瘤中Snail表达的减少和口腔黑色素瘤中Snail表达的增加有关，表明N-钙黏着蛋白与Snail表达之间的相关性与肿瘤的位置一致。我们的数据表明，ZEB家族蛋白与N-钙粘蛋白从细胞膜到细胞质和细胞核的转运有关，并且可能是犬黑色素瘤EMT调控的重要转录因子。