Gronnier Caroline, Bruyère Emilie, Lahdaoui Fatima, Jonckheere Nicolas, Perrais Michaël, Leteurtre Emmanuelle, Piessen Guillaume, Mariette Christophe, Van Seuningen Isabelle
Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France.
Biochim Biophys Acta. 2014 Nov;1843(11):2432-7. doi: 10.1016/j.bbamcr.2014.06.021. Epub 2014 Jul 6.
MUC1 is a membrane-bound mucin known to participate in tumor proliferation. It has been shown that MUC1 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplasia to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is gastro-esophageal reflux and MUC1 was previously shown to be up-regulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC1 plays a role in biological properties of human esophageal cancer cells. For that, a stable MUC1-deficient esophageal cancer cell line was established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of MUC1-deficient cells were analyzed. Our results show that esophageal cancer cells lacking MUC1 were less proliferative and had decreased migration and invasion properties. These alterations were accompanied by a decreased activity of NFKB p65, Akt and MAPK (p44/42, JNK and p38) pathways. MCM6 and TSG101 tumor-associated markers were also decreased. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC1. Altogether, the data indicate that MUC1 plays a key role in proliferative, migrating and invasive properties of esophageal cancer cells as well as in tumor growth promotion. MUC1 mucin appears thus as a good therapeutic target to slow down esophageal tumor progression.
MUC1是一种已知参与肿瘤增殖的膜结合粘蛋白。研究表明，在食管癌发生过程中，MUC1的表达模式会发生改变，从化生到腺癌呈逐渐增加的趋势。食管腺癌发生发展的主要原因是胃食管反流，先前研究表明，反流中存在的几种胆汁酸可上调MUC1的表达。因此，在本报告中，我们旨在确定MUC1是否在人食管癌细胞的生物学特性中发挥作用。为此，我们采用shRNA方法建立了稳定的MUC1缺陷食管癌细胞系。分析了MUC1缺陷细胞的体外（增殖、迁移和侵袭）和体内（SCID小鼠皮下异种移植后的肿瘤生长）生物学特性。我们的结果表明，缺乏MUC1的食管癌细胞增殖能力较弱，迁移和侵袭特性降低。这些改变伴随着NFKB p65、Akt和MAPK（p44/42、JNK和p38）信号通路活性的降低。MCM6和TSG101肿瘤相关标志物也减少。当细胞不表达MUC1时，皮下异种移植瘤的大小显著减小。总之，这些数据表明，MUC1在食管癌细胞的增殖、迁移和侵袭特性以及促进肿瘤生长方面发挥着关键作用。因此，MUC1粘蛋白似乎是减缓食管肿瘤进展的良好治疗靶点。
