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

Abstract

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 Iγ phosphatidylinositol phosphate kinase (PIPKIγ) 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 PIPKIγ expression is upregulated in multiple epithelial ovarian cancer cell lines. Silencing of PIPKIγ impaired PI3K/AKT signaling and inhibited the aggressive behaviors of epithelial ovarian cancer cells, including proliferation, migration and invasion. Moreover, we found that PIPKIγ 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 PIPKIγ-dependent aggressiveness of epithelial ovarian cancer cells. Our results, for the first time, identified PIPKIγ 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 PIPKIγ 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.

Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer

“…All three PIP5K isoforms play significant roles in actin remodeling events and various cellular functions, including protein trafficking, cell division and locomotion. Recent evidence has indicated the involvement of PIP5Ks in cancer progression, such as in prostate cancer ( 45 , 46 ), ovarian cancer ( 47 ), and notably, breast cancer ( 48 , 49 ). Given the critical role of PI(4,5)P2 in regulating cellular events and its contribution to tumor cell invasion and migration, the implication of PIP5Ks in breast cancer is a compelling avenue for investigation.…”