The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells DOI Creative Commons
Georgios Kalampounias, Kalliopi Zafeiropoulou, Theodosia Androutsopoulou

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(5), С. 352 - 352

Опубликована: Май 12, 2025

The rapid emergence of resistance limits the application proteasome inhibitors against solid tumors, despite their effectiveness in treatment hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, mechanisms involved have not been adequately described. In this study, a Bortezomib-resistant prostate cancer cell line is created by using PC-3 as carcinoma model high metastatic potential. main biochemical differences adaptations exhibited resistant cells revolve around apoptosis evasion, autophagy induction (functioning ubiquitin-proteasome system substitute), expression epithelial-to-mesenchymal transition markers, increased aggressiveness. Broad-spectrum signaling pathway analyses also reveal an upregulation activation Nf-κB, STAT3, cJun, Elk1 transcription factors cells. Additionally, intracellular reactive oxygen species assays downregulation cells, which theorized to be consequence metabolic changes, autophagic flux, antioxidative enzyme action. These findings expand our understanding inhibitor highlight key kinases novel potential therapeutic targets. Effective inhibition resistance-specific pathways could re-sensitize inhibitors, thus surpassing current limitations.

Язык: Английский

The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells DOI Creative Commons
Georgios Kalampounias, Kalliopi Zafeiropoulou, Theodosia Androutsopoulou

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(5), С. 352 - 352

Опубликована: Май 12, 2025

The rapid emergence of resistance limits the application proteasome inhibitors against solid tumors, despite their effectiveness in treatment hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, mechanisms involved have not been adequately described. In this study, a Bortezomib-resistant prostate cancer cell line is created by using PC-3 as carcinoma model high metastatic potential. main biochemical differences adaptations exhibited resistant cells revolve around apoptosis evasion, autophagy induction (functioning ubiquitin-proteasome system substitute), expression epithelial-to-mesenchymal transition markers, increased aggressiveness. Broad-spectrum signaling pathway analyses also reveal an upregulation activation Nf-κB, STAT3, cJun, Elk1 transcription factors cells. Additionally, intracellular reactive oxygen species assays downregulation cells, which theorized to be consequence metabolic changes, autophagic flux, antioxidative enzyme action. These findings expand our understanding inhibitor highlight key kinases novel potential therapeutic targets. Effective inhibition resistance-specific pathways could re-sensitize inhibitors, thus surpassing current limitations.

Язык: Английский

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