Cellular prion protein promotes invasion and metastasis of gastric cancer
Cellular prion protein promotes invasion and metastasis of gastric cancer
复制标题
DOI：
10.1096/fj.06-6138fje
复制
发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Pan, Yanglin;Zhao, Lina;Fan, Daiming
PrPc是一种糖基化磷脂酰肌醇(GPI)锚定的膜蛋白，在哺乳动物中高度保守。PrPC具有黏附分子的特性，被认为在细胞黏附和膜信号转导中发挥作用。在这里，我们研究了PrPc在胃癌侵袭和转移过程中的可能作用。免疫组织化学染色发现PrPC在转移性胃癌中高表达，而在非转移性胃癌中高表达。PrPC显著促进胃癌细胞株SGC7901和MKN45的黏附、侵袭和体内转移能力。PrPC还通过激活磷酸化的ERK1/2，增加胃癌细胞的启动子活性和MMP11的表达。MEK抑制剂PD98059和MMP11抗体可显著抑制PrPc诱导的体外侵袭和体内转移能力。N-末端片段(24-90位氨基酸)是PrPc信号转导和侵袭促进功能不可缺少的区域。综上所述，本工作揭示了PrPc的一个新功能，即PrPc的N末端区域的存在至少部分地通过激活MEK/ERK通路和随后的MMP11反式激活来促进胃癌细胞的侵袭和转移能力。-潘勇、赵力、梁杰、刘杰、施勇、刘宁、张戈、金、H.、高、J.、谢、H.、王杰、刘、Z.、范、D.细胞蛋白促进胃癌的侵袭和转移。
Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI) - anchored membrane protein that is highly conserved in mammalian species. PrPc has the characteristics of adhesive molecules and is thought to play a role in cell adhesion and membrane signaling. Here we investigated the possible role of PrPc in the process of invasiveness and metastasis in gastric cancers. PrPc was found to be highly expressed in metastatic gastric cancers compared to nonmetastatic ones by immunohistochemical staining. PrPc significantly promoted the adhesive, invasive, and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45. PrPc also increased promoter activity and the expression of MMP11 by activating phosphorylated ErK1/2 in gastric cancer cells. MEK inhibitor PD98059 and MMP11 antibody (Ab) significantly inhibited in vitro invasive and in vivo metastatic abilities induced by PrPc. N-terminal fragment (amino acid 24 - 90) was suggested to be an indispensable region for signal transduction and invasion-promoting function of PrPc. Taken together, the present work revealed a novel function of PrPc that the existence of N-terminal region of PrPc could promote the invasive and metastatic abilities of gastric cancer cells at least partially through activation of MEK/ERK pathway and consequent transactivation of MMP11. - Pan, Y., Zhao, L., Liang, J., Liu, J., Shi, Y., Liu, N., Zhang, G., Jin, H., Gao, J., Xie, H., Wang, J., Liu, Z., Fan, D. Cellular prion protein promotes invasion and metastasis of gastric cancer.