TY  - EJOU
AU  - Matei, Elena 
AU  - Iorga, Ionuț Ciprian 
AU  - Deacu, Mariana 
AU  - Cozaru, Georgeta Camelia 
AU  - Băltățescu, Gabriela Isabela 
AU  - Enciu, Manuela 

TI  - Dysregulated Cell Signaling Pathways in Prostate Tumoral Plasticity—Checkpoints
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b><i>Objectives:</i></b> Deregulated plasticity is involved in initiation, progression, metastasis, and resistance to therapy of various cancers. Our study aimed to present new checkpoints involved in complex biological processes that sustain epithelial-mesenchymal transition (EMT) variability and heterogeneity in prostate tumor cell plasticity. <b><i>Methods:</i></b> Dysregulated cell signaling pathways involved in prostate EMT heterogeneity were analyzed by intrinsic and extrinsic factors such as cell cycle phases by propidium iodide (PI) stain, apoptosis by caspase-3/7 biochemical cascade DEVDase enzyme activity by Magic Red stain (DEVD-MR)/propidium iodide stain, autophagy and nuclear shrinkage by Hoechst/acridine orange stain, evasion of immune surveillance by GPIba platelet glycoprotein conjugated with phycoerythrin (CD42b-PE) stain, oxidative stress by total reactive oxygen species (ROS) count by flow cytometry. Adaptation of the microenvironment involved in prostate EMT heterogeneity was analyzed by immunohistochemistry (IHC). <b><i>Results:</i></b> In our study, in benign prostatic hyperplasia (BPH) tissue samples, the low S-proliferative phase category of the cell cycle (SH: &lt;7%) represents an independent predictor and a favorable prognostic biomarker for patient survival, as it is reported to dysregulate cell signaling pathways that characterize EMT heterogeneity. In prostate cancer tissue samples (PCa), the high S-proliferative phase category of the cell cycle (SCA, &gt;12%) had an unfavorable prognostic role in patient survival rate, characteristically for EMT heterogeneity and aggressive phenotype involved in prostate tumoral cell plasticity, serving as a dependent predictor for the molecular mechanisms network, including late apoptosis, necrosis, autophagy, evasion of immune surveillance, cell cycle arrest in G0/G1 or G2/M phases, and oxidative stress. <b><i>Conclusion:</i></b> Low and high S-proliferative phase categories of the cell cycle, dysregulated early, late apoptosis via caspase-3/7 signaling pathway represent important checkpoints involved in EMT heterogeneity, and serve as independent or dependent predictor biomarkers for BPH and PCa patient prognostic survival rates, targeting personalized cancer therapy development.
KW  - Epithelial-mesenchymal transition (EMT); necrosis-apoptosis continuum; DNA damage; transcription factor p53; autophagy; microenvironment

DO  - 10.32604/or.2026.072421