Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion.
Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion.
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DOI：
10.3892/or.2017.5670
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发表时间：
2017-07
期刊：
影响因子：
4.2
通讯作者：
Ling K
中科院分区：
文献类型：
--
作者：
Cao S;Chen C;Xue J;Huang Y;Yang X;Ling K
转移是卵巢癌患者死亡的主要原因。鉴于转移形成的分子机制对于改善治疗开发和临床治疗至关重要，因此必须充分理解。近年来研究发现，I型脂激酶γ磷脂酰肌醇磷酸激酶（lipid kinase type Iγ phosphatidylinositol phosphate kinase，PIPKIγ）通过调节细胞迁移和侵袭，参与乳腺癌和结肠癌的转移。然而，其在卵巢癌进展中的作用尚不清楚。在此，我们发现PIPKIγ表达在多种上皮性卵巢癌细胞系中上调。PIPKIγ的沉默可抑制PI 3 K/AKT信号通路，抑制卵巢癌细胞的增殖、迁移和侵袭等侵袭行为。此外，我们发现PIPKIγ是上皮性卵巢癌细胞中信号转导子和转录激活子3（STAT 3）激活所必需的，表明STAT 3也可能参与上皮性卵巢癌细胞的PIPKIγ依赖性侵袭。我们的研究结果首次将PIPKIγ鉴定为上皮性卵巢癌细胞中的一种新型调节因子，通过激活多种信号通路促进细胞增殖、迁移和侵袭。因此，我们建议PIPKIγ可能成为早期检测和治疗上皮性卵巢癌的治疗靶点。采用体内模型的进一步研究是必要的，以测试这种可能性。
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.