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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qian Chen ◽  
Lu Li ◽  
Xian Liu ◽  
Qian Feng ◽  
Yanru Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Distant Metastasis ◽  
Tumor Metastasis ◽  
Sequencing Analysis ◽  
Mmp9 Expression ◽  
Cervical Cancer Cells ◽  
Squamous Cervical Carcinoma

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.

scholarly journals Hexokinases 2 Promoted Cell Motility and Distant Metastasis by Elevating Fibronectin Through Akt1/p-Akt1 in Cervical Cancer Cells

2021 ◽  
Author(s):  
Qian Chen ◽  
Lu Li ◽  
Xian Liu ◽  
Qian Feng ◽  
Yanru Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Distant Metastasis ◽  
Tumor Metastasis ◽  
Sequencing Analysis ◽  
Mmp9 Expression ◽  
Cervical Cancer Cells ◽  
Squamous Cervical Carcinoma

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 detected 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.

scholarly journals Absence of EpCAM in cervical cancer cells is involved in slug induced epithelial-mesenchymal transition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xian Liu ◽  
Qian Feng ◽  
Yanru Zhang ◽  
PengSheng Zheng ◽  
Nan Cui
Keyword(s):  
Cervical Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Negative Correlation ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Suppression Effect ◽  
Epcam Expression ◽  
Cervical Cancer Cells ◽  
E Cadherin

Abstract Background Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study. Methods RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation. Results Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis. Conclusions These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.

Muscarinic cholinergic signaling in cervical cancer cells affects cell motility via ERK1/2 signaling

Life Sciences ◽  
2012 ◽  
Vol 91 (21-22) ◽  
pp. 1093-1098 ◽  
Author(s):  
Erinn A. Parnell ◽  
Itzel E. Calleja-Macias ◽  
Mina Kalantari ◽  
Sergei A. Grando ◽  
Hans-Ulrich Bernard
Keyword(s):  
Cervical Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cholinergic Signaling ◽  
Cervical Cancer Cells ◽  
Muscarinic Cholinergic

scholarly journals Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells

2003 ◽  
Vol 77 (2) ◽  
pp. 1551-1563 ◽  
Author(s):  
Rosa Anna DeFilippis ◽  
Edward C. Goodwin ◽  
Lingling Wu ◽  
Daniel DiMaio
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Carcinoma Cells ◽  
Rb Pathway ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
E7 Proteins ◽  
E6 Protein

ABSTRACT Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins, and repression of HPV gene expression causes the cells to cease proliferation and undergo senescence. However, it is not known whether both HPV proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. To address these questions, we used the bovine papillomavirus E2 protein to repress the expression of either the E6 protein or the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells. Repression of the E7 protein activated the Rb pathway but not the p53 pathway and triggered senescence, whereas repression of the E6 protein activated the p53 pathway but not the Rb pathway and triggered both senescence and apoptosis. Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc were markedly inhibited by repression of either E6 or E7. These results demonstrate that continuous expression of both the E6 and the E7 protein is required for optimal proliferation of cervical carcinoma cells and that the two viral proteins exert distinct effects on cell survival and proliferation. Therefore, strategies that inhibit the expression or activity of either viral protein are likely to inhibit the growth of HPV-associated cancers.

scholarly journals Absence of EpCAM in Cervical Cancer Cells Is Involved in Slug-induced Epithelial-mesenchymal Transition

2020 ◽  
Author(s):  
Xian Liu ◽  
Feng Qian ◽  
Yanru Zhang ◽  
Pengsheng Zheng ◽  
Nan Cui
Keyword(s):  
Cervical Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Negative Correlation ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Suppression Effect ◽  
Epcam Expression ◽  
Cervical Cancer Cells ◽  
E Cadherin

Abstract Background: Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study. The positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study.Methods: RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation.Results: Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis.Conclusions: These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.

scholarly journals The endonuclease APE1 processes miR-92b formation, thereby regulating expression of the tumor suppressor LDLR in cervical cancer cells

2019 ◽  
Vol 11 ◽  
pp. 175883591985585 ◽  
Author(s):  
Yi Sun ◽  
Yun Feng ◽  
Guiqian Zhang ◽  
Ya Xu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Cell Cycle Progression ◽  
Endonuclease Activity ◽  
Cycle Progression ◽  
Cervical Cancer Cells ◽  
Novel Therapeutic

Background: The molecular mechanisms underlying cervical cancer require elucidation to identify novel therapeutic targets. Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is a multifunctional apurinic/apyrimidinic (AP) endonuclease that influences the transcription of many cancer-related genes via microRNome regulation. Herein, we examine the role of miR-92b-3p (hereinafter miR-92b), whose processing may be regulated by APE1, in cervical cancer progression. Methods: APE1’s processing of miR-92b from its pri-miR form was measured by a quantitative reverse transcription polymerase chain reaction (qRT-PCR)-based ratio. APE1’s endonuclease activity was measured with AP-site incision assays. APE1-DROSHA interaction was studied with immunofluorescence, confocal and proximity ligation analyses. The miR-92b’s targeting of low-density lipoprotein receptor (LDLR) was investigated with luciferase reporter assays. The miR-92b mimics and shRNA-based miR-92b silencing, as well as LDLR overexpression and short interfering RNA (siRNA)-based LDLR silencing, were employed in CaSki and SiHa cervical cancer cells. Cell proliferation and chemosensitivity to paclitaxel and cisplatin were assayed. Cell-cycle progression and apoptosis were assessed by flow cytometry. Tumor growth was studied in a murine xenograft model. Results: APE1’s endonuclease activity, via association with the DROSHA-processing complex, is necessary for processing mature miR-92b, thereby regulating expression of miR-92b’s direct target LDLR. The miR-92b promotes cell proliferation in vitro and in vivo, promotes cell-cycle progression, and reduces apoptosis and chemosensitivity. LDLR silencing recapitulated miR-92b’s transformative effects, while LDLR overexpression rescued these effects. Conclusions: APE1 enhances miR-92b processing, thereby suppressing LDLR expression and enhancing cervical carcinoma progression. Our identification of the novel APE1-miR-92b-LDLR axis improves our understanding of the complex pathogenesis of cervical carcinoma and reveals a novel therapeutic strategy for combating this disease.

Sign in / Sign up

Export Citation Format

Share Document