Sequential events during the quiescence to proliferation transition establish patterns of follicle cell differentiation in the Drosophila ovary DOI Creative Commons
Eric H. Lee, Daniel Zinshteyn,

Fred Miglo

et al.

Biology Open, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 16, 2022

Stem cells cycle between periods of quiescence and proliferation to promote tissue health. In Drosophila ovaries, transitions follicle stem (FSCs) are exquisitely feeding-dependent. Here, we demonstrate feeding-dependent induction cell differentiation markers, eyes absent (Eya) castor (Cas) in FSCs, a patterning process that does not depend on induction. Instead, FSCs extend micron-scale cytoplasmic projections dictate Eya-Cas patterning. We identify still life sickie as necessary sufficient for FSC projection growth Our results suggest sequential, interdependent events establish long-term patterns precursors, independently

Language: Английский

Valosin‐Containing Protein (VCP/p97) Mediates Neuroendocrine Differentiation in Prostate Cancer Cells Through Pim1 Signaling Inducing Autophagy DOI

K Sruthi,

Ramesh Ummanni

The Prostate, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

ABSTRACT Background Neuroendocrine Prostate Cancer (NEPC) is an aggressive type of androgen‐independent prostate cancer (AIPC) associated with resistance to treatment. Valosin‐containing protein (VCP/p97) has been found be overexpressed in (PCa) cells undergoing neuroendocrine differentiation (NED) response interleukin‐6 (IL‐6). This study explores the molecular mechanisms through which VCP/p97 contributes progression NEPC. Methods To investigate role NED PCa, we PCa cells. The underlying induced were assessed by using western blot analysis and RT‐PCR. Morphological changes analyzed both bright field confocal microscope. Lysotracker staining was performed identify autophagy VCP positive Results In present study, that expression notably higher (NE) NCI‐H660 PC3 than other IL‐6 treatment led significant overexpression LNCaP VCaP cells, a marked increase NE markers NSE CHR‐A. Inhibition NMS‐873 attenuated features, suggesting required for progression. Moreover, VCP's linked its regulation via Pim1 differentiating Exogenous enhanced c‐Myc expression, diminished upon inhibition corroborated reduced markers. AZD1208 knockdown further supported Pim1's involvement mediated NED. promote NED, regulated autophagy, as evidenced increased LC3B decreased SQSTM1/p62 levels overexpression. or disrupted autophagic flux, arresting flux assays confirmed enhancing lysosomal‐mediated autophagolysosome formation. Furthermore, show AMPK activation, LKB1 essential autophagy. Conclusion drives complex interplay involving axis pathways. These findings highlight potential targeting therapeutic strategies inhibit

Language: Английский

Citations

0
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

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 352 - 352

Published: May 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.

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
A novel selective estrogen receptor degrader induces cell cycle arrest in breast cancer via ERα degradation and the autophagy-lysosome pathway DOI
Jiawei Zhou, Rong Shen, Jing Liu

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 82, P. 117235 - 117235

Published: March 1, 2023

Language: Английский

Citations

6
Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research DOI

Dara M. Ruiz-Whalen,

Christopher P. Aichele,

Ebony R. Dyson

et al.

Methods in molecular biology, Journal Year: 2023, Volume and Issue: unknown, P. 399 - 444

Published: Jan. 1, 2023

Language: Английский

Citations

1
Bioinformatics-based Investigation of Autophagy-Related Biomarkers in Heritable Ovarian Carcinoma DOI Creative Commons
Zhimin Wang,

Jia Ning Liu,

Nan-xiang Sun

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 3, 2024

Abstract Objective To investigate the role of autophagy-related genes (ARGs) in Heritable Ovarian Carcinoma (HOC) and identify potential biomarkers therapeutic targets. Methods We conducted a comprehensive bioinformatics-based analysis gene expression patterns 420 HOC samples 7 normal tissues. Differential 17 ARGs out 232 candidate was identified. Functional annotation pathway enrichment analyses were performed to explore biological functions these ARGs. A prognostic model based on 11 survival-associated established validated. Results Our revealed differentially expressed tissues, suggesting their as diagnostic biomarkers. GO KEGG indicated involvement critical processes signaling pathways. The demonstrated promising predictive capabilities for patient outcomes HOC. Conclusion findings shed light significance provide targets improved this heritable ovarian carcinoma.

Language: Английский

Citations

0
Sequential events during the quiescence to proliferation transition establish patterns of follicle cell differentiation in the Drosophila ovary DOI Creative Commons
Eric H. Lee, Daniel Zinshteyn,

Fred Miglo

et al.

Biology Open, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 16, 2022

Stem cells cycle between periods of quiescence and proliferation to promote tissue health. In Drosophila ovaries, transitions follicle stem (FSCs) are exquisitely feeding-dependent. Here, we demonstrate feeding-dependent induction cell differentiation markers, eyes absent (Eya) castor (Cas) in FSCs, a patterning process that does not depend on induction. Instead, FSCs extend micron-scale cytoplasmic projections dictate Eya-Cas patterning. We identify still life sickie as necessary sufficient for FSC projection growth Our results suggest sequential, interdependent events establish long-term patterns precursors, independently

Language: Английский

Citations

0