Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells

Abstract Background Hexokinases 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....

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Autores principales:	Qian Chen, Lu Li, Xian Liu, Qian Feng, Yanru Zhang, Pengsheng Zheng, Nan Cui
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	HK2 Fibronectin (FN1) Akt1 Metastasis Cervical cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/d511d91c8360454c882ebccac57eb4b6
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spelling	oai:doaj.org-article:d511d91c8360454c882ebccac57eb4b62021-11-14T12:37:38ZHexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells10.1186/s12935-021-02312-01475-2867https://doaj.org/article/d511d91c8360454c882ebccac57eb4b62021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02312-0https://doaj.org/toc/1475-2867Abstract Background Hexokinases 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. Methods In 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. Results In 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. Conclusions This 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.Qian ChenLu LiXian LiuQian FengYanru ZhangPengsheng ZhengNan CuiBMCarticleHK2Fibronectin (FN1)Akt1MetastasisCervical cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HK2 Fibronectin (FN1) Akt1 Metastasis Cervical cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	HK2 Fibronectin (FN1) Akt1 Metastasis Cervical cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Qian Chen Lu Li Xian Liu Qian Feng Yanru Zhang Pengsheng Zheng Nan Cui Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
description	Abstract Background Hexokinases 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. Methods In 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. Results In 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. Conclusions This 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.
format	article
author	Qian Chen Lu Li Xian Liu Qian Feng Yanru Zhang Pengsheng Zheng Nan Cui
author_facet	Qian Chen Lu Li Xian Liu Qian Feng Yanru Zhang Pengsheng Zheng Nan Cui
author_sort	Qian Chen
title	Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
title_short	Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
title_full	Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
title_fullStr	Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
title_full_unstemmed	Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells
title_sort	hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through akt1/p-akt1 in cervical cancer cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d511d91c8360454c882ebccac57eb4b6
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Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells

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