Abstract
BackgroundHexokinases 2 (HK2) is a member of the hexokinases, linking with malignant tumor growth and distant metastasis. However, evidence regarding the potential role of HK2 in regulating cell motility and tumor metastasis during the cervical cancer malignant progression remains limited.MethodsIn vitro migration and invasion assay, in vivo metastasis experiments were performed to detect the effective of HK2 on regulating cell motility and tumor metastasis in cervical cancer cells. RNA-Seq was performed to explore the potential molecules that participate in HK2-mediated cell motility and tumor metastasis in cervical cancer cells. The correlation between HK2 and Akt1, p-Akt1, FN1 expression in cervical cancer cells and human squamous cervical carcinoma (SCC) samples was verified in this study.ResultsIn this study, cervical cancer cells with exogenous HK2 expression exhibited enhanced cell motility and distant metastasis. Transcriptome sequencing analysis revealed that fibronectin (FN1) was significantly increased in HK2-overexpressing HeLa cells, and the PI3K/Akt signaling pathway was identified by KEGG pathway enrichment analysis. Further studies demonstrated that this promotion of cell motility by HK2 was probably a result of it inducing FN1, MMP2 and MMP9 expression by activating Akt1 in cervical cancer cells. Additionally, HK2 expression was altered with the changing of Akt1/p-Akt1 expression, implying that HK2 expression is also modulated by Akt1/p-Akt1. Moreover, the positive correlation between HK2 and Akt1, p-Akt1, FN1 expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis.ConclusionsThis study demonstrated that HK2 could activate Akt1 in cervical cancer cells, subsequently enhancing cell motility and tumor metastasis by inducing FN1, MMP2 and MMP9 expression. There likely exists an interactive regulatory mechanism between HK2 and Akt1 during the malignant process of cervical cancer.
Highlights
Hexokinases 2 (HK2) is a member of the hexokinases, linking with malignant tumor growth and distant metastasis
This study demonstrated that HK2 could activate Akt1 in cervical cancer cells, subsequently enhancing cell motility and tumor metastasis by inducing FN1, Matrix metalloproteinase-2 (MMP2) and Matrix metalloproteinase-9 (MMP9) expression
HK2 promotes cell migration and invasion of cervical cancer cells in vitro Data from the GEPIA online database revealed that HK2 expression was much higher in cervical cancer tissues than in normal tissues (Additional file 1: Fig. S1A), and such increased HK2 was associated with poor prognosis in cervical cancer patients (Additional file 1: Fig. S1B)
Summary
Hexokinases 2 (HK2) is a member of the hexokinases, linking with malignant tumor growth and distant metastasis. Evidence regarding the potential role of HK2 in regulating cell motility and tumor metastasis during the cervical cancer malignant progression remains limited. Cervical cancer is the fourth most common malignant tumor in the world. It is the most common female reproductive system tumor. FN1 is an established marker for epithelial-mesenchymal transition (EMT), and stimulated FN1 expression has been observed in various types of cancer and is associated with enhanced cell migration, invasion and tumor metastasis [4, 5]. Aberrant FN1 expression was confirmed to be involved in cell viability, apoptosis, migration and invasion [8]
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