title: Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells.
abstract: High-grade serous ovarian cancer is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D023102:Anoikis; D001343:Autophagy; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010537:Peritoneum / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016392:Proto-Oncogene Proteins pp60(c-src); D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases