scholarly journals CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

2021 ◽  
Author(s):  
Xian Lin ◽  
Feng Wang ◽  
Jing Liu ◽  
Yibin Lin ◽  
Li Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Wnt Signaling ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Recurrence ◽  
Cancer Stemness ◽  
Mesenchymal Transition ◽  
P53 Signaling ◽  
Damage Repair

Abstract Background Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression. Methods Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip. Results CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis. Conclusions This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.

scholarly journals P4HA2 contributes to cervical cancer progression via inducing epithelial-mesenchymal transition

2020 ◽  
Vol 11 (10) ◽  
pp. 2788-2799
Author(s):  
Yuan Cao ◽  
Qicai Han ◽  
Juan Li ◽  
Yanyan Jia ◽  
Ruitao Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

EphB2 promotes cervical cancer progression by inducing epithelial-mesenchymal transition

2014 ◽  
Vol 45 (2) ◽  
pp. 372-381 ◽  
Author(s):  
Qing Gao ◽  
Wei Liu ◽  
Jiangyi Cai ◽  
Mu Li ◽  
Yane Gao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence

2021 ◽  
Author(s):  
Samatha Bhat ◽  
Divya Adiga ◽  
Vaibhav Shukla ◽  
Kanive Parashiva Guruprasad ◽  
Shama Prasada Kabekkodu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Vesicle Trafficking ◽  
Critical Role ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Intracellular Vesicle

AbstractSenescence induction and epithelial-mesenchymal transition (EMT) events are the opposite sides of the spectrum of cancer phenotypes. The key molecules involved in these processes may get influenced or altered by genetic and epigenetic changes during tumor progression. Double C2-like domain beta (DOC2B), an intracellular vesicle trafficking protein of the double C2 protein family, plays a critical role in exocytosis, neurotransmitter release, and intracellular vesicle trafficking. DOC2B is repressed by DNA promoter hypermethylation and functions as a tumor growth regulator in cervical cancer. To date, the molecular mechanisms of DOC2B in cervical cancer progression and metastasis is elusive. Herein, the biological functions and molecular mechanisms regulated by DOC2B and its impact on senescence and EMT are described. DOC2B inhibition promotes proliferation, growth, and migration by relieving G0/G1-S arrest, actin remodeling, and anoikis resistance in Cal27 cells. It enhanced tumor growth and liver metastasis in nude mice with the concomitant increase in metastasis-associated CD55 and CD61 expression. Inhibition of EMT and promotion of senescence by DOC2B is a calcium-dependent process and accompanied by calcium-mediated interaction between DOC2B and CDH1. In addition, we have identified several EMT and senescence regulators as targets of DOC2B. We show that DOC2B may act as a metastatic suppressor by inhibiting EMT through induction of senescence via DOC2B-calcium-EMT-senescence axis. Graphical abstract

scholarly journals Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition

Oncotarget ◽  
2016 ◽  
Vol 7 (15) ◽  
pp. 19631-19642 ◽  
Author(s):  
Jienan Kong ◽  
Chunchan Di ◽  
Junjie Piao ◽  
Jie Sun ◽  
Longzhe Han ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Absence of miR-378d Promoted The Malignant Phenotype of ESCC Through The AKT-β-Catenin and Hippo-p53 Signaling Pathway

2020 ◽  
Author(s):  
Jie Peng ◽  
Juan Yu ◽  
Jianli Liu ◽  
Haixiang Wei ◽  
Haixia Song ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Marker ◽  
Poor Prognostic Factor ◽  
P53 Expression ◽  
Mesenchymal Transition ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: Chemoresistance is an important cause of malignant progression of esophageal squamous cell carcinomas (ESCCs). miR-378d is sharply reduced in paclitaxel (PTX)-resistance esophageal cancer cells by gene-expression profile analysis (RNA-Seq), but the mechanism of miR-378d-mediated tumor progression is unclear. Patients and methods: Herein, we detected miR-378d expression in 596 ESCC patients by in situ hybridization. Results showed that low miR-378d expression was associated with poor prognosis of ESCC patients, and that miR-378d absence enhanced carcinogenesis by promoting chemoresistance, colony formation, EMT, invasion, and metastasis. Results: Furthermore, miR-378d can target downregulated AKT1 expression by binding to the AKT1 mRNA 3′UTR, inactivating the AKT-β-catenin signaling pathway, and reducing the epithelial–mesenchymal transition marker Vimentin and the cancer stem cell marker ALDH1A1. miR-378d silencing in ESCC cells also promoted polyploidy formation in vitro and in vivo, and miR-378d inhibition suppressed the Hippo-p53 signaling pathway. Consequnetly, YAP and TAZ protein accumulated in nuclei and p53 expression decreased, which may promote the formation of ploidy tumor cells. Conclusions: Therefore, low miR-378d expression is a poor prognostic factor of ESCC patients and promotes polyploidy and cancer progression by activating AKT-β-catenin and suppressing the Hippo-p53 signaling pathway.

scholarly journals Mitofusin-2 Promotes the Epithelial-Mesenchymal Transition-Induced Cervical Cancer Progression

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Sung Yong Ahn ◽  
Jiwon Song ◽  
Yu Cheon Kim ◽  
Myoung Hee Kim ◽  
Young-Min Hyun
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mitofusin 2 ◽  
Mesenchymal Transition

scholarly journals Roles of Non-Coding RNAs in Cervical Cancer Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tanchun Cheng ◽  
Shouguo Huang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Interaction Network ◽  
Mesenchymal Transition ◽  
Complex Process ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Huge Challenge

Metastasis remains to be a huge challenge in cancer therapy. The mechanism underlying cervical cancer metastasis is not well understood and needs to be elucidated. Recent studies have highlighted the diverse roles of non-coding RNAs in cancer progression and metastasis. Increasing numbers of miRNAs, lncRNAs and circRNAs are found to be dysregulated in cervical cancer, associated with metastasis. They have been shown to regulate metastasis through regulating metastasis-related genes, epithelial-mesenchymal transition, signaling pathways and interactions with tumor microenvironment. Moreover, miRNAs can interact with lncRNAs and circRNAs respectively during this complex process. Herein, we review literatures up to date involving non-coding RNAs in cervical cancer metastasis, mainly focus on the underlying mechanisms and highlight the interaction network between miRNAs and lncRNAs, as well as circRNAs. Finally, we discuss the therapeutic prospects.

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