The ERK1/2-Elk1, JNK-cJun, and JAK-STAT Transcriptional Axes as Potential Bortezomib Resistance Mediators in Prostate Cancer DOI Creative Commons
Georgios Kalampounias, Kalliopi Zafeiropoulou, Theodosia Androutsopoulou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 20, 2024

Abstract The effectiveness of proteasome inhibitors against solid tumors is limited as the emergence resistance rapid. Although many mechanisms have been proposed and verified, no definite answer has given, highlighting complexity resistant phenotype. In this study, a Bortezomib-resistant prostate cancer cell line created, broad-spectrum signaling pathway analysis performed to identify differences adaptations cells exhibit. Our findings highlight upregulation activation Nf-κB, STAT3, cJun, Elk1 transcription factors in subsequent evasion apoptosis induction autophagy, which constantly activated substitutes role ubiquitin-proteasome system (UPS). Additionally, assessment intracellular reactive oxygen species confirms their downregulation, theorized be consequence metabolic changes, increased autophagic flux, antioxidative enzyme action. results study potential therapeutic targeting key kinases factors, participating main pathways gene regulation cells, that could re-sensitize inhibitors, thus surpassing current limitations.

Language: Английский

Dihydromyricetin restores lysosomal function in Schwann cells to alleviate bortezomib-induced peripheral neuropathy via ERK/TFEB signaling DOI
Xiaoliang Liu, Xingxian Zhang, Xinhang Li

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 6, 2025

Language: Английский

Citations

0
The ERK1/2-Elk1, JNK-cJun, and JAK-STAT Transcriptional Axes as Potential Bortezomib Resistance Mediators in Prostate Cancer DOI Creative Commons
Georgios Kalampounias, Kalliopi Zafeiropoulou, Theodosia Androutsopoulou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 20, 2024

Abstract The effectiveness of proteasome inhibitors against solid tumors is limited as the emergence resistance rapid. Although many mechanisms have been proposed and verified, no definite answer has given, highlighting complexity resistant phenotype. In this study, a Bortezomib-resistant prostate cancer cell line created, broad-spectrum signaling pathway analysis performed to identify differences adaptations cells exhibit. Our findings highlight upregulation activation Nf-κB, STAT3, cJun, Elk1 transcription factors in subsequent evasion apoptosis induction autophagy, which constantly activated substitutes role ubiquitin-proteasome system (UPS). Additionally, assessment intracellular reactive oxygen species confirms their downregulation, theorized be consequence metabolic changes, increased autophagic flux, antioxidative enzyme action. results study potential therapeutic targeting key kinases factors, participating main pathways gene regulation cells, that could re-sensitize inhibitors, thus surpassing current limitations.

Language: Английский

Citations

2