Adenosinergic Signalling in Cervical Cancer Microenvironment

Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5′-nucleotidase (CD73/5′-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations...

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Published inExpert reviews in molecular medicine Vol. 27; p. e5
Main Authors Iser, Isabele Cristiana, Bertoni, Ana Paula Santin, Beckenkamp, Liziane Raquel, Consolaro, Marcia Edilaine Lopes, Maria-Engler, Silvya Stuchi, Wink, Marcia Rosângela
Format Journal Article
LanguageEnglish
Published Cambridge, UK Cambridge University Press 07.01.2025
Subjects
5'-Nucleotidase - genetics
5'-Nucleotidase - metabolism
adenosine
Adenosine - metabolism
Adenosine diphosphate
adenosine kinase
Adenosine triphosphate
Animals
Cancer therapies
Cancer vaccines
CD73
CD73 antigen
Cell adhesion & migration
Cell death
Cell growth
Cervical cancer
DNA methylation
Enzymes
Epigenetics
Female
Glioma
GPI-Linked Proteins - genetics
GPI-Linked Proteins - metabolism
Human papillomavirus
Humans
Kinases
Metastasis
methylation
NT5E
Nucleotidase
Phosphatase
Review
Signal Transduction - genetics
Tumor microenvironment
Tumor Microenvironment - genetics
Tumors
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
adenosine
CD73
NT5E
adenosine kinase
cervical cancer
methylation
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Abstract Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5′-nucleotidase (CD73/5′-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.
AbstractList Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5′-nucleotidase (CD73/5′-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.
Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5'-nucleotidase (CD73/5'-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5'-nucleotidase (CD73/5'-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.
Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5′-nucleotidase (CD73/5′-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.
Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5'-nucleotidase (CD73/5'-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.
ArticleNumber e5
Author Beckenkamp, Liziane Raquel
Wink, Marcia Rosângela
Iser, Isabele Cristiana
Bertoni, Ana Paula Santin
Maria-Engler, Silvya Stuchi
Consolaro, Marcia Edilaine Lopes
AuthorAffiliation 1 Department of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto Alegre , Porto Alegre , RS , Brazil
3 Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo , São Paulo , SP , Brazil
2 Department of Clinical Analysis and Biomedicine, Division of Clinical Cytology, State University of Maringá , Maringá , PR , Brazil
AuthorAffiliation_xml – name: 1 Department of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto Alegre , Porto Alegre , RS , Brazil
– name: 3 Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo , São Paulo , SP , Brazil
– name: 2 Department of Clinical Analysis and Biomedicine, Division of Clinical Cytology, State University of Maringá , Maringá , PR , Brazil
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  organization: 1Department of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
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  surname: Maria-Engler
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  organization: 1Department of Basics Health Sciences and Laboratory of Cell Biology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
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Keywords adenosine
CD73
NT5E
adenosine kinase
cervical cancer
methylation
Language English
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Isabele Cristiana Iser and Ana Paula Santin Bertoni have contributed equally to this paper.
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2022; 174
2013; 2
2010; 107
2019; 11
2000; 87
2010; 101
2020; 17
2017; 390
2020; 16
2020; 15
2014; 25
2005; 65
2012; 18
2008; 33
2020; 10
2017; 276
2003; 278
2016; 37
2022; 27
2018; 47
2018; 7
2009; 11
2023; 256–257
2018; 2
2015; 137
2019; 20
2023; 570
2013; 57
1991; 88
2022; 40
2014; 15
2019; 27
2000; 362
2019; 393
2017; 320
2012; 23
2012; 22
2012; 20
2023; 72
2019; 8
2015; 56
2018; 29
2019; 4
2020; 42
2019; 36
2014; 2014
1999; 189
2024; 14
2012; 106
2014; 45
2016; 14
2012; 107
2016; 12
2016; 11
2023; 41
2016; 2
2014; 307
2022; 8
2005; 7
2022; 14
2020; 24
2022; 10
2022; 11
2016; 29
1973; 8
2012; 359
2016; 8
2018; 14
2003; 23
2018; 13
2017; 8
2019; 56
2024; 81
1987; 6
2022; 69
2020; 57
2002; 119
2012; 59
2017; 9
2017; 118
2013; 18
2014; 5
2023; 24
2021; 31
2014; 4
2017; 36
2020; 130
2013; 13
2021; 39
2008; 319
2019; 479
2019; 118
2021; 41
2014; 6
2007; 26
2003; 89
2021; 505
2021; 7
2018; 144
1990; 75
2014; 92
2023; 14
2021; 4
2023; 11
2010; 79
2015; 93
2015; 10
1998; 338
2008; 12
2016; 126
2019; 145
2018; 68
2022; 158
2021; 13
2012; 1
2017; 17
2021; 17
2002; 21
1970; 45
2016; 63
2008; 82
2012; 8
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Snippet Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly....
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SubjectTerms 5'-Nucleotidase - genetics
5'-Nucleotidase - metabolism
adenosine
Adenosine - metabolism
Adenosine diphosphate
adenosine kinase
Adenosine triphosphate
Animals
Cancer therapies
Cancer vaccines
CD73
CD73 antigen
Cell adhesion & migration
Cell death
Cell growth
Cervical cancer
DNA methylation
Enzymes
Epigenetics
Female
Glioma
GPI-Linked Proteins - genetics
GPI-Linked Proteins - metabolism
Human papillomavirus
Humans
Kinases
Metastasis
methylation
NT5E
Nucleotidase
Phosphatase
Review
Signal Transduction - genetics
Tumor microenvironment
Tumor Microenvironment - genetics
Tumors
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
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Title Adenosinergic Signalling in Cervical Cancer Microenvironment
URI https://www.cambridge.org/core/product/identifier/S1462399424000309/type/journal_article
https://www.ncbi.nlm.nih.gov/pubmed/39762204
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Volume 27
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