己糖激酶 2 通过激活人卵巢癌细胞中的 Akt1/p-Akt1 促进细胞迁移和增殖。
Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells.
机构信息
Department of Obstetrics and Gynecology/Centre for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Endocrinology, Xijing 986 Hospital, Fourth Military Medical University, Xi'an, 710032, China.
出版信息
J Ovarian Res. 2022 Aug 11;15(1):92. doi: 10.1186/s13048-022-01027-8.
BACKGROUND
Recently, increasing evidence has indicated that elevation of Hexokinase 2 (HK2) plays an important role in several cancers on regulating cell motility and growth. However, its role on regulating cell EMT in human ovarian cancer still less to known.
METHODS
The transwell and wound-healing assay were used to detect the effective of HK2 on regulating motility of ovarian cancer cells. Real Time PCR and Western Blotting were used to explore the changing of EMT-related proteins in HK2-modified cells. The clonogenic formation, cell growth curves and MTT assays were used to evaluate the effective of HK2 on regulating cell proliferation in HK2-modified cells. The flow cytometry was used to detect the differences in the distribution of cells in the cell cycle between the HK2-modified cells and their control cells. The correlation of HK2 and Akt1/p-Akt1 was explored by using Western Blotting, Akt1 inhibitor (MK2206) and transient transfection of an Akt1 recombinant plasmid. The potential correlation between HK2 and EMT-related proteins in human ovarian cancer tissues and OV (ovarian serous cystadenocarcinoma) was confirmed by using Pearson correlation analysis and TIMER 2.0.
RESULTS
In ovarian cancer cells, overexpressing of HK2 enhanced cell motility by inducing of EMT-related proteins, such as CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin. Moreover, overexpressing of HK2 promoted cell growth by reducing p21 and p27 expression in ovarian cancer cells. Further studies demonstrated that this promotion of cell motility and growth by HK2 was probably a result of it activating of Akt1 (p-Akt1) in ovarian cancer cells. Additionally, the positive correlation between HK2 and p-Akt1, fibronectin, MMP9 expression in human ovarian cancer samples was verified by using Pearson correlation analysis. The positive correlation between HK2 and CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin in OV (ovarian serous cystadenocarcinoma) was confirmed by using TIMER 2.0.
CONCLUSION
This study demonstrated that HK2 could induce EMT-related proteins and reduce cell cycle inhibitor by activating Akt1 in human ovarian cancer cells, subsequently enhancing cell motility and growth, suggesting that HK2 participate in the malignant process of ovarian cancer by interacting with Akt1.
背景
最近，越来越多的证据表明，己糖激酶 2（HK2）的升高在调节细胞运动和生长方面在几种癌症中起着重要作用。然而，其在调节人卵巢癌中细胞 EMT 中的作用仍知之甚少。
方法
使用 Transwell 和划痕愈合实验检测 HK2 对卵巢癌细胞运动能力的影响。实时 PCR 和 Western Blotting 用于探索 HK2 修饰细胞中 EMT 相关蛋白的变化。克隆形成、细胞生长曲线和 MTT 分析用于评估 HK2 对 HK2 修饰细胞中细胞增殖的影响。流式细胞术用于检测 HK2 修饰细胞与其对照细胞之间细胞周期中细胞分布的差异。通过 Western Blotting、Akt1 抑制剂（MK2206）和 Akt1 重组质粒的瞬时转染来探索 HK2 与 Akt1/p-Akt1 的相关性。通过 Pearson 相关性分析和 TIMER 2.0 证实了 HK2 与人类卵巢癌组织和 OV（卵巢浆液性囊腺癌）中 EMT 相关蛋白之间的潜在相关性。
结果
在卵巢癌细胞中，过表达 HK2 通过诱导 EMT 相关蛋白，如 CDH2、纤连蛋白、MMP9、ZEB1、ZEB2 和波形蛋白，增强细胞运动能力。此外，过表达 HK2 通过降低卵巢癌细胞中 p21 和 p27 的表达促进细胞生长。进一步的研究表明，HK2 通过激活卵巢癌细胞中的 Akt1（p-Akt1）促进细胞运动和生长。此外，通过 Pearson 相关性分析验证了人类卵巢癌样本中 HK2 与 p-Akt1、纤连蛋白、MMP9 表达之间的正相关性。通过 TIMER 2.0 证实了 HK2 与 OV（卵巢浆液性囊腺癌）中 CDH2、纤连蛋白、MMP9、ZEB1、ZEB2 和波形蛋白之间的正相关性。
结论
本研究表明，HK2 通过激活 Akt1 在人卵巢癌细胞中诱导 EMT 相关蛋白并降低细胞周期抑制剂，从而增强细胞运动和生长，表明 HK2 通过与 Akt1 相互作用参与卵巢癌的恶性过程。
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