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酪蛋白激酶1δ调节人卵巢癌细胞的细胞增殖、化疗反应和迁移。

Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells.

作者信息

Mazzoldi Elena Laura, Pastò Anna, Ceppelli Elisa, Pilotto Giorgia, Barbieri Vito, Amadori Alberto, Pavan Simona

机构信息

Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy.

Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

出版信息

Front Oncol. 2019 Nov 12;9:1211. doi: 10.3389/fonc.2019.01211. eCollection 2019.

Abstract

Casein kinase 1 delta (CK1δ) has a tumor-promoting role in different cancers and it is genetically amplified in a portion of human epithelial ovarian cancer (EOC). CK1δ is involved in pleiotropic cellular functions such as cell proliferation, DNA damage, and migration. We specifically knocked down CK1δ by short hairpin RNA (shRNA) in human ovarian cancer cells and we performed proliferation, chemosensitivity, as well as and migration assays. CK1δ knocked-down cells displayed reduced proliferation capability both and . Nonetheless, these cells were sensitized to the first line chemotherapeutic agent carboplatin (CPT), and this observation could be associated to reduced expression levels of p21(Cip1/Waf1), involved in DNA damage response, and the anti-apoptotic X-linked inhibitor of apoptosis protein (XIAP). Moreover, CK1δ knocked-down cells were affected in their migratory and lung homing capability, even if in opposite ways, i.e., IGROV1, SKOV3 and MES-OV lost, while OVCAR3 gained motility potential. The results suggest CK1δ as a potential exploitable target for pharmacological EOC treatment, but they also advise further investigation of its role in cell migration.

摘要

酪蛋白激酶1δ(CK1δ)在不同癌症中具有促肿瘤作用,并且在一部分人上皮性卵巢癌(EOC)中发生基因扩增。CK1δ参与多种细胞功能,如细胞增殖、DNA损伤和迁移。我们通过短发夹RNA(shRNA)在人卵巢癌细胞中特异性敲低CK1δ,并进行了增殖、化学敏感性以及迁移实验。敲低CK1δ的细胞在[具体两种情况未明确写出]中均表现出增殖能力降低。尽管如此,这些细胞对一线化疗药物卡铂(CPT)敏感,这一观察结果可能与参与DNA损伤反应的p21(Cip1/Waf1)以及抗凋亡的X连锁凋亡抑制蛋白(XIAP)表达水平降低有关。此外,敲低CK1δ的细胞的迁移和肺归巢能力受到影响,尽管方式相反,即IGROV1、SKOV3和MES-OV失去迁移能力,而OVCAR3获得运动潜能。结果表明CK1δ是EOC药物治疗的一个潜在可利用靶点,但也建议进一步研究其在细胞迁移中的作用。

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