Cellular prion protein promotes invasion and metastasis of gastric cancer.
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
Yanglin
Y
State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changle Western Rd., Xi'an, Shaanxi Province, 710032, PR China.
Zhao
Lina
L
Liang
Jie
J
Liu
Jie
J
Shi
Yongquan
Y
Liu
Na
N
Zhang
Guoyun
G
Jin
Haifeng
H
Gao
Juan
J
Xie
Huahong
H
Wang
Jun
J
Liu
Zhiguo
Z
Fan
Daiming
D
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002448:Cell Adhesion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009930:Organic Chemicals / Q000494:pharmacology; D011328:Prions / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D005419:Flavonoids; D018960:Hyaluronan Receptors; D009930:Organic Chemicals; D011328:Prions; C113282:prinomastat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one