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Verfasst von:Strobel, Tobias [VerfasserIn]   i
 Weber, Maria [VerfasserIn]   i
 Heber, Nora [VerfasserIn]   i
 Holzer, Angela [VerfasserIn]   i
 Hoppe-Seyler, Karin [VerfasserIn]   i
 Hoppe-Seyler, Felix [VerfasserIn]   i
Titel:Revisiting the role of endogenous STAT3 in HPV-positive cervical cancer cells
Verf.angabe:Tobias D. Strobel, Maria Weber, Nora Heber, Angela Holzer, Karin Hoppe-Seyler, Felix Hoppe-Seyler
E-Jahr:2023
Jahr:November 2023
Umfang:18 S.
Illustrationen:Illustrationen
Fussnoten:Zuerst veröffentlicht: 27. November 2023 ; Gesehen am 04.06.2024
Titel Quelle:Enthalten in: Journal of medical virology
Ort Quelle:Bognor Regis [u.a.] : Wiley, 1977
Jahr Quelle:2023
Band/Heft Quelle:95(2023), 11, Artikel-ID e29230, Seite 1-18
ISSN Quelle:1096-9071
Abstract:Novel treatment options for human papillomavirus (HPV)-induced cancers are urgently required. The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is considered to be constitutively active in HPV-positive cervical cancer cells and essential for their proliferation. Moreover, STAT3 was reported to undergo mutually stimulatory interactions with the HPV E6/E7 oncogenes. Thus, inhibiting STAT3 in HPV-positive cancer cells is under discussion to provide a powerful novel therapeutic strategy. We here show that the antifungal drug ciclopirox destabilizes the STAT3 protein by acting as an iron chelator. However, by exploring the functional consequences of STAT3 inhibition in HPV-positive cancer cells, we obtained several unexpected results. Chemical STAT3 inhibitors heterogeneously affect cervical cancer cell proliferation and those which act antiproliferative also block the growth of STAT3 knockout cells, indicating induction of off-target effects. In contrast to several chemical inhibitors, genetic inhibition of STAT3 expression by either RNA interference or the CRISPR/Cas9 method does not appreciably affect cervical cancer cell proliferation. Transcriptome analyses indicate that blocking STAT3 expression in HPV-positive cancer cells has very limited effects on putative STAT3 target genes. Although the targeted inhibition of specific growth-promoting signaling pathways leads to a feedback activation of STAT3 in cervical cancer cells via Janus kinase 1/2, this does not lead to treatment resistance. Moreover, we did not obtain experimental evidence for a STAT3-linked activation of HPV E6/E7 oncogene expression or, vice versa, an E6/E7-dependent activation of STAT3, at endogenous conditions in cervical cancer cells. Collectively, these findings question the essential role of STAT3 in cervical cancer cell proliferation and the strategy to inhibit STAT3 in these cells for therapeutic purposes.
DOI:doi:10.1002/jmv.29230
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1002/jmv.29230
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.29230
 DOI: https://doi.org/10.1002/jmv.29230
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cervical cancer
 ciclopirox
 human papillomavirus
 MEK
 PI3K
 STAT3
K10plus-PPN:1890591483
Verknüpfungen:→ Zeitschrift

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