Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion

Metastasis is the major cause of death in ovarian cancer patients. Given that the molecular mechanism underlying metastasis formation is critical for improving therapeutic development and clinical treatment, it must be fully understood. Recent studies have revealed that lipid kinase type I gamma phosphatidylinositol phosphate kinase (PIPKI gamma) participates in the metastasis of breast cancer and colon cancer by regulating cell migration and invasion. However, its role in the progression of ovarian cancer is unclear. Here we showed that PIPKI gamma expression is upregulated in multiple epithelial ovarian cancer cell lines. Silencing of PIPKI gamma impaired PI3K/AKT signaling and inhibited the aggressive behaviors of epithelial ovarian cancer cells, including proliferation, migration and invasion. Moreover, we found that PIPKI gamma was required for the activation of signal transducer and activator of transcription 3 (STAT3) in epithelial ovarian cancer cells, indicating that STAT3 may also be engaged in the PIPKI gamma-dependent aggressiveness of epithelial ovarian cancer cells. Our results, for the first time, identified PIPKI gamma as a novel regulator in epithelial ovarian cancer cells that promotes cell proliferation, migration and invasion by activating multiple signaling pathways. Therefore, we propose that PIPKI gamma could potentially be a therapeutic target for the early detection and treatment of epithelial ovarian cancer. Further studies employing in vivo models are necessary to test this possibility.