| RRC ID |
42779
|
| 著者 |
Koizume S, Jin MS, Miyagi E, Hirahara F, Nakamura Y, Piao JH, Asai A, Yoshida A, Tsuchiya E, Ruf W, Miyagi Y.
|
| タイトル |
Activation of cancer cell migration and invasion by ectopic synthesis of coagulation factor VII.
|
| ジャーナル |
Cancer Res
|
| Abstract |
Blood coagulation factor VII (fVII) is physiologically synthesized in the liver and released into the blood. Binding of fVII to tissue factor (TF) at sites of vascular injury triggers coagulation and hemostasis. TF/fVIIa complex formation on the surface of cancer cells plays important roles in cancer biology. Although fVII is synthesized by hepatocellular carcinoma, it remained unclear how TF/fVIIa complex formation and promigratory signaling can occur for most other cancers in extravascular locations. Here, we show by reverse transcription-PCR analysis that nonhepatic cancer cell lines constitutively express fVII mRNA and that endogenously synthesized fVIIa triggers coagulation activation on these cells. fVIIa expression in cancer cells is inducible under hypoxic conditions and hypoxia-inducible factor-2 alpha bound the promoter region of the FVII gene in chromatin immunoprecipitation analyses. Constitutive fVII expression in an ovarian cancer cell line enhanced both migration and invasion. Enhanced motility was blocked by anti-TF antibodies, factor Xa inhibition, and anti-protease-activated receptor-1 antibody treatment, confirming that TF/fVIIa stimulated migration by triggering cell signaling. This study shows that ectopic synthesis of fVII by cancer cells is sufficient to support proinvasive factor Xa-mediated protease-activated receptor-1 signaling and that this pathway is inducible under hypoxia.
|
| 巻・号 |
66(19)
|
| ページ |
9453-60
|
| 公開日 |
2006-10-1
|
| DOI |
10.1158/0008-5472.CAN-06-1803
|
| PII |
66/19/9453
|
| PMID |
17018600
|
| MeSH |
Basic Helix-Loop-Helix Transcription Factors / physiology
Blood Coagulation
Carbon-Carbon Ligases / biosynthesis
Carbon-Carbon Ligases / genetics
Cell Hypoxia / genetics
Cell Line, Tumor / metabolism
Cell Movement / physiology
Factor VII / biosynthesis*
Factor VII / genetics
Factor VII / physiology
Factor Xa / physiology
Female
Humans
Neoplasm Invasiveness / physiopathology*
Neoplasm Proteins / biosynthesis*
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology
Neoplasms / blood
Neoplasms / pathology
Ovarian Neoplasms / pathology
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
RNA, Neoplasm / biosynthesis
RNA, Neoplasm / genetics
Receptor, PAR-1 / physiology
Recombinant Fusion Proteins / physiology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Thromboplastin / biosynthesis
Thromboplastin / genetics
Transfection
|
| IF |
9.727
|
| 引用数 |
104
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
OCUB-M(RCB0881)
MDA-MB-453(RCB1192) |
