Tréhoux Solange, Duchêne Bélinda, Jonckheere Nicolas, Van Seuningen Isabelle
Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France.
Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France.
Biochem Biophys Res Commun. 2015 Jan 16;456(3):757-62. doi: 10.1016/j.bbrc.2014.12.025. Epub 2014 Dec 13.
MUC1 is an oncogenic mucin overexpressed in several epithelial cancers, including pancreatic ductal adenocarcinoma, and is considered as a potent target for cancer therapy. To this aim, we undertook to study MUC1 biological effects on pancreatic cancer cells and identify pathways mediating these effects. Our in vitro experiments indicate that inhibiting MUC1 expression decreases cell proliferation, cell migration and invasion, cell survival and increases cell apoptosis. Moreover, lack of MUC1 in these cells profoundly altered their sensitivity to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. In vivo MUC1-KD cell xenografts in SCID mice grew slower. Altogether, we show that MUC1 oncogenic mucin alters proliferation, migration, and invasion properties of pancreatic cancer cells and that these effects are mediated by p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways.
MUC1是一种致癌粘蛋白，在包括胰腺导管腺癌在内的几种上皮癌中过表达，被认为是癌症治疗的有效靶点。为此，我们着手研究MUC1对胰腺癌细胞的生物学效应，并确定介导这些效应的途径。我们的体外实验表明，抑制MUC1表达可降低细胞增殖、细胞迁移和侵袭、细胞存活并增加细胞凋亡。此外，这些细胞中MUC1的缺失深刻改变了它们对吉西他滨和5-氟尿嘧啶化疗药物的敏感性。在SCID小鼠体内，MUC1-KD细胞异种移植生长较慢。总之，我们表明MUC1致癌粘蛋白改变了胰腺癌细胞的增殖、迁移和侵袭特性，并且这些效应是由p42-44 MAPK、Akt、Bcl-2和MMP13途径介导的。
