dc.contributor.author
Higareda-Almaraz, Juan Carlos
dc.contributor.author
Ruiz-Moreno, Juan S.
dc.contributor.author
Klimentova, Jana
dc.contributor.author
Barbieri, Daniela
dc.contributor.author
Salvador-Gallego, Raquel
dc.contributor.author
Ly, Regina
dc.contributor.author
Valtierra-Gutierrez, Ilse A.
dc.contributor.author
Dinsart, Christiane
dc.contributor.author
Rabinovich, Gabriel A.
dc.contributor.author
Stulik, Jiri
dc.contributor.author
Roesl, Frank
dc.contributor.author
Rincon-Orozco, Bladimiro
dc.date.accessioned
2018-06-08T03:29:10Z
dc.date.available
2016-11-04T09:27:58.997Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/15283
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19471
dc.description.abstract
Background Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and
appears to be a link between the apoptotic response triggered by cancer and
the anti-tumoral activity of the immune system. Our understanding of how
cervical cancer cells and their molecular networks adapt in response to the
expression of Gal-7 remains limited. Methods Meta-analysis of Gal-7 expression
was conducted in three cervical cancer cohort studies and TCGA. In silico
prediction and bisulfite sequencing were performed to inquire epigenetic
alterations. To study the effect of Gal-7 on cervical cancer, we ectopically
re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed
their transcriptome and SILAC-based proteome. We also examined the tumor and
microenvironment host cell transcriptomes after xenotransplantation into
immunocompromised mice. Differences between samples were assessed with the
Kruskall-Wallis, Dunn’s Multiple Comparison and T tests. Kaplan–Meier and log-
rank tests were used to determine overall survival. Results Gal-7 was
constantly downregulated in our meta-analysis (p < 0.0001). Tumors with
combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented
significantly better prognoses (p = 0.005). In silico and bisulfite sequencing
assays showed de novo methylation in the Gal-7 promoter and first intron.
Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their
xenografts displayed strong growth retardation (p < 0.001). Multiple gene
modules and transcriptional regulators were modulated in response to Gal-7
reconstitution, both in cervical cancer cells and their microenvironments (FDR
< 0.05 %). Most of these genes and modules were associated with tissue
morphogenesis, metabolism, transport, chemokine activity, and immune response.
These functional modules could exert the same effects in vitro and in vivo,
even despite different compositions between HeLa and SiHa samples. Conclusions
Gal-7 re-expression affects the regulation of molecular networks in cervical
cancer that are involved in diverse cancer hallmarks, such as metabolism,
growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends
to the microenvironment, where networks involved in its configuration and in
immune surveillance are particularly affected.
de
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Cervical cancer
dc.subject
Differential network analysis
dc.subject
Microenvironment crosstalk
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer
and its microenvironment
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
BMC Cancer. - 16 (2016), Artikel Nr. 680
dcterms.bibliographicCitation.doi
10.1186/s12885-016-2700-8
dcterms.bibliographicCitation.url
http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2700-8
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000025671
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000007314
dcterms.accessRights.openaire
open access