ETV7 reduces inflammatory responses in breast cancer cells by repressing the TNFR1/NF-κB axis.

Autor: Meškytė EM; Laboratory of Molecular Cancer Genetics, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.; Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania., Pezzè L; Laboratory of Molecular Cancer Genetics, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.; Alia Therapeutics, s.r.l., Trento, Italy., Bartolomei L; Laboratory of Radiobiology, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Forcato M; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy., Bocci IA; Laboratory of Molecular Cancer Genetics, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.; Institut für Zellbiologie, Universitätsklinikum Essen, Essen, Germany., Bertalot G; Unità Operativa Multizonale di Anatomia Patologica, APSS, Trento, Italy.; Centre for Medical Sciences (CISMed), University of Trento, Trento, Italy., Barbareschi M; Unità Operativa Multizonale di Anatomia Patologica, APSS, Trento, Italy.; Centre for Medical Sciences (CISMed), University of Trento, Trento, Italy., Oliveira-Ferrer L; Gynecology Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bisio A; Laboratory of Radiobiology, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Bicciato S; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy., Baltriukienė D; Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania., Ciribilli Y; Laboratory of Molecular Cancer Genetics, Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy. yari.ciribilli@unitn.it.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2023 Apr 12; Vol. 14 (4), pp. 263. Date of Electronic Publication: 2023 Apr 12.
DOI: 10.1038/s41419-023-05718-y
Abstrakt: The transcription factor ETV7 is an oncoprotein that is up-regulated in all breast cancer (BC) types. We have recently demonstrated that ETV7 promoted breast cancer progression by increasing cancer cell proliferation and stemness and was also involved in the development of chemo- and radio-resistance. However, the roles of ETV7 in breast cancer inflammation have yet to be studied. Gene ontology analysis previously performed on BC cells stably over-expressing ETV7 demonstrated that ETV7 was involved in the suppression of innate immune and inflammatory responses. To better decipher the involvement of ETV7 in these signaling pathways, in this study, we identified TNFRSF1A, encoding for the main receptor of TNF-α, TNFR1, as one of the genes down-regulated by ETV7. We demonstrated that ETV7 directly binds to the intron I of this gene, and we showed that the ETV7-mediated down-regulation of TNFRSF1A reduced the activation of NF-κB signaling. Furthermore, in this study, we unveiled a potential crosstalk between ETV7 and STAT3, another master regulator of inflammation. While it is known that STAT3 directly up-regulates the expression of TNFRSF1A, here we demonstrated that ETV7 reduces the ability of STAT3 to bind to the TNFRSF1A gene via a competitive mechanism, recruiting repressive chromatin remodelers, which results in the repression of its transcription. The inverse correlation between ETV7 and TNFRSF1A was confirmed also in different cohorts of BC patients. These results suggest that ETV7 can reduce the inflammatory responses in breast cancer through the down-regulation of TNFRSF1A.
(© 2023. The Author(s).)
Databáze: MEDLINE
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