title: Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK-PI3K/Akt pathway.
abstract: Ovarian cancer is the leading cause of death from gynecological malignancy, and the fourth most common cause of cancer death among American women. This study investigates the mechanism of fibronectin (FN) in stimulating ovarian cancer cell migration and invasion through up-regulation of focal adhesion kinase (FAK) pathway. Human ovarian cancer cells (OVCAR-3, A2780/CP70) were cultured and treated with fibronectin (10 µg/mL). Trans-well plates were used to conduct the migration assay, real-time RT-PCR for FAK mRNA expression, and FAK siRNA for blocking FAK expression. Western blots were used for P-FAK, P-PI3K, and P-Akt analysis. Fibronectin-treated OVCAR-3, A2780/CP70 cells have increased ability to migrate and invade. It significantly promoted this behavior through the phosphorylation of FAK. The cell displayed significantly increased signaling regulation of the FAK pathway (p-PI3K/P-Akt). Furthermore, siRNA FAK-treated cells had reduced the levels of p-PI3K/P-Akt after induced by fibronectin. Our results indicate that FAK inhibition can suppress ovarian cancer cells migration and invasion through inhibiting downstream signaling (PI3K/AKT), which might be a therapeutic target or biomarker for ovarian cancer.
authors.affiliation: Department of Medicine and Surgery, University of Colorado Denver, Denver, Colorado, 80045, USA.
authors.forename: Nasser Ghaly
authors.initials: NG
authors.lastname: Yousif
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D005353:Fibronectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: cancer; cell adhesion; cell migration; matrix metalloproteinases