MUC1与肿瘤:信号通路和临床研究

MUC1是一种异源二聚体跨膜糖蛋白,由氮端亚单位(MUC1-N)和碳端亚单位(MUC1-C)组成。MUC1在多种上皮来源的肿瘤组织中异常表达,其与肿瘤的发生发展密切相关。MUC1-N可与细胞间黏附分子-1、E-选择素和半乳凝素-3相互作用并且通过MUC1-C调节信号传导,MUC1-C可与表皮生长因子受体家族和其他酪氨酸激酶受体相互作用并且参与PI3K→AKT、MAP、NF-κB、Wnt、STAT、P53和Erα信号通路,因此MUC1与肿瘤的增殖、侵袭转移和化疗耐药密切相关。本研究阐述了MUC1-N和MUC1-C与其他分子相互作用以及在激活肿瘤相关信号通路中的作用,最后回顾了MUC1-N单抗、MUC1-C小分子肽和MUC1疫苗在临床试验阶段的研究情况。

胃癌组织及区域淋巴结MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系

背景与目的:研究证实胃癌浸润深度和淋巴结转移是多基因及其蛋白表达产物协调作用的结果,寻找与胃癌转移相关的分子生物学标志物有助于胃癌的研究。本实验旨在探讨胃癌组织及区域淋巴结中MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系。方法:采用SP免疫组织化学方法对110例胃癌组织及613枚区域淋巴结中的MUC1、CD44v6、nm23基因蛋白的表达进行检测。结果:①胃癌组织中的MUC1蛋白阳性表达在低分化癌组、浸润型组、T3+T4组、淋巴结转移组、Ⅲ～Ⅳ期组、生存期<5年组分别为84.6%、88.1%、87.3%、91.7%、94.4%、95.5%,CD44v6分别为79.5%、74.6%、79.4%、81.7%、87.0%、87.9%,nm23分别为38.5%、32.2%、30.2%、25.0%、25.9%、18.2%。MUC1和CD44v6表达低分化癌组显著高于高、中分化癌组(78.9%vs57.7%),浸润型组高于局限型组(72.6%vs54.9%),T3+T4组高于T2组(72.3%vs46.8%),淋巴结转移组高于无淋巴结转移组(68.0%vs46.0%),TNMⅢ～Ⅳ期组高于Ⅰ～Ⅱ期组(67.9%vs44.6%),生存期<5年组高于≥5年组(59.1%vs31.8%),各组间差异均具有显著性(P<0.01或P<0.05)。而nm23除分化程度、Borrmann分型不同的两组之间差异无显著性外,T3+T4组低于T2组(51.1%),有淋巴结转移组低于无淋巴结转移组(56.0%)。

Inhibition of KL-6/MUC1 glycosylation limits aggressive progression of pancreatic cancer

AIM:To evaluate the significance of KL-6/MUC1(a type of MUC1)glycosylation in pancreatic cancer progression.METHODS:KL-6/MUC1 expression was detected by immunohistochemistry in 48 patients with pancreatic duct cell carcinoma.The N-/O-glycosylation inhibitors(tunicamycin and benzyl-N-acetyl-α-galactosaminide)were then used to interfere with KL-6/MUC1 glycosylation in two pancreatic carcinoma cell lines,and the effects on KL-6/MUC1 expression,and cell adhesion and invasion were determined.In addition,protein expression of epithelial-mesenchymal transition markers,E-cadherin and vimentin,were evaluated in cells after treatment with glycosylation inhibitors.RESULTS:Overexpression of KL-6/MUC1 was found in all pancreatic cancer tissues,but not in the surrounding normal pancreatic tissues.The expression profile of KL-6/MUC1 was significantly decreased after treatment with the inhibitors.The adhesion and invasive ability of cancer cells were significantly decreased after drug treatment,and increased E-cadherin and decreased vimentin expression were found.CONCLUSION:KL-6/MUC1 glycosylation is involved in pancreatic cancer metastasis and invasion.Therapeutic strategies which target this may help control the aggressive behavior of pancreatic cancer cells.