Krüppel-Like Factor 10 participates in cervical cancer immunoediting through transcriptional regulation of Pregnancy-Specifc Beta-1 Glycoproteins
Cervical cancer (CC) is currently the second most common cancer among the female population1 . As is the case with many other cancer types, host immune system evasion, involving the failure of the immune system to resist or eradicate formation and progression of incipient neoplastic cells, late-s...
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Format: | Artículo |
Language: | English |
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2018
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Online Access: | https://doi.org/10.1038/s41598-018-27711-8 https://www.nature.com/articles/s41598-018-27711-8 |
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Summary: | Cervical cancer (CC) is currently the second most common cancer among the female population1
. As is the case
with many other cancer types, host immune system evasion, involving the failure of the immune system to resist
or eradicate formation and progression of incipient neoplastic cells, late-stage tumors and micro-metastasis is
problematic in CC2
. Te host immune response evasion by Human Papilloma Virus (HPV) associated CC has
been reviewed elsewhere3
. Cytokines such as Interleukin (IL) 10, IL13 and transforming growth factor β (TGFβ)
are known to be involved in evasion of CC from the immune system response3,4
. Tumor-associated infammation
and the infammatory components present in the tumor microenvironment are also recognized as having a role
in tumor development5
. Tis is mediated in part through the supply of bioactive molecules to the tumor microenvironment.
Tese include growth factors, survival factors, pro-angiogenic factors, extracellular matrix-modifying
enzymes, as well as the inductive signals that lead to activation of epithelial-mesenchymal transition (EMT)2
. Tis
phenomenon is orchestrated by a plethora of cytokines and chemokines. In CC, cytokines such as IL6, −86
and Cervical cancer (CC) is currently the second most common cancer among the female population1
. As is the case
with many other cancer types, host immune system evasion, involving the failure of the immune system to resist
or eradicate formation and progression of incipient neoplastic cells, late-stage tumors and micro-metastasis is
problematic in CC2
. Te host immune response evasion by Human Papilloma Virus (HPV) associated CC has
been reviewed elsewhere3
. Cytokines such as Interleukin (IL) 10, IL13 and transforming growth factor β (TGFβ)
are known to be involved in evasion of CC from the immune system response3,4
. Tumor-associated infammation
and the infammatory components present in the tumor microenvironment are also recognized as having a role
in tumor development5
. Tis is mediated in part through the supply of bioactive molecules to the tumor microenvironment.
Tese include growth factors, survival factors, pro-angiogenic factors, extracellular matrix-modifying
enzymes, as well as the inductive signals that lead to activation of epithelial-mesenchymal transition (EMT)2
. Tis
phenomenon is orchestrated by a plethora of cytokines and chemokines. In CC, cytokines such as IL6, −86
and Cervical cancer (CC) is currently the second most common cancer among the female population1
. As is the case
with many other cancer types, host immune system evasion, involving the failure of the immune system to resist
or eradicate formation and progression of incipient neoplastic cells, late-stage tumors and micro-metastasis is
problematic in CC2
. Te host immune response evasion by Human Papilloma Virus (HPV) associated CC has
been reviewed elsewhere3
. Cytokines such as Interleukin (IL) 10, IL13 and transforming growth factor β (TGFβ)
are known to be involved in evasion of CC from the immune system response3,4
. Tumor-associated infammation
and the infammatory components present in the tumor microenvironment are also recognized as having a role
in tumor development5
. Tis is mediated in part through the supply of bioactive molecules to the tumor microenvironment.
Tese include growth factors, survival factors, pro-angiogenic factors, extracellular matrix-modifying
enzymes, as well as the inductive signals that lead to activation of epithelial-mesenchymal transition (EMT)2
. Tis
phenomenon is orchestrated by a plethora of cytokines and chemokines. In CC, cytokines such as IL6, −86
and as well as chemokines such as CCL28
are known to exert these pro-infammatory efects. Expression of these
molecules in the tumor microenvironment is tightly regulated by transcription factors.
Krüppel like factors (KLF’s) are a family of transcription factors that participate in various aspects of cellular
growth, proliferation and diferentiation9
. Tis family is characterized by three C2H2-type zinc fnger domains
that bind to either CACCC elements or GC boxes in the promoter of target genes to regulate transcriptional activity
and gene expression9
. Recently, we have reported the expression of several members of the KLF family in CC
including KLF1010. KLF10 can function as a trans-activator or –repressor11. It has been previously reported that
KLF10 is expressed in several tissues and various cell types that include smooth muscle, heart, glial cells, fbroblasts,
myeloid cells12, and lymphoid cells11. Gene-targeting studies have implicated important roles for KLFs in
immune and hematopoietic cell biology. For example, in CD4+CD25− cells, KLF10 is known to play an important
role in T-cell activation and diferentiation as well as Treg suppressor functions through regulation of TGFβ11. It
has been reported that KLF10 can also directly regulate the pro-infammatory cytokine IL12p4013.
In addition to the above-mentioned functions of KLF10 in multiple cell and tissue types, no one has implicated
a role for KLF10 in CC. In this report we have analyzed the molecular alterations of KLF10 in CC and have identifed
potential KLF10 target genes by means of DNA copy number variation (CNV) and mRNA transcription
using microarrays, in silico analyses and putative transcriptional regulatory networks using gene knock-down
approaches in vitro and in vivo. |
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