title: Inhibition of IGF-1-Mediated Cellular Migration and Invasion by Migracin A in Ovarian Clear Cell Carcinoma Cells.
abstract: Previously we isolated migracin A from a Streptomyces culture filtrate as an inhibitor of cancer cell migration. In the present research, we found that migracin A inhibited migration and invasion of ovarian clear cell carcinoma ES-2 cells. In the course of our mechanistic study, migracin A was shown to enhance vasohibin-1 expression in an angiogenesis array. We also confirmed that it increased the mRNA expression of this protein. Moreover, overexpression of vasohibin-1 lowered the migration but not the invasion of ES-2 cells. Then, we looked for another target protein employing a motility array, and found that migracin A lowered the IGF-1 expression. Knockdown of IGF-1 by siRNA decreased the migration and invasion of ES-2 cells. Migracin A also decreased Akt phosphorylation involved in the downstream signaling. Crosstalk analysis indicated that overexpression of vasohibin-1 decreased the IGF-1 expression. On the other hand, it showed no direct anticancer activity in terms of the ES-2 growth in agar. Migracin A inhibited the migration and IGF-1 expression in not only ES-2 but also another ovarian clear cell carcinoma JHOC-5 cells. In addition, it also inhibited capillary tube formation of human umbilical vein endothelial cells. Since its cytotoxicity is very low, migracin A may be a candidate for an anti-metastasis agent not exhibiting prominent toxicity.
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute, 480-1195, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Ukaji
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute, 480-1195, Japan.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute, 480-1195, Japan.
authors.forename: Shoshiro
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute, 480-1195, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism*; D001547:Benzaldehydes / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020543:Proteome; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014410:Tumor Stem Cell Assay
chemical_list: D001547:Benzaldehydes; D018797:Cell Cycle Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D020543:Proteome; C493181:VASH1 protein, human; C582003:migracin A; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt