Open Access
ARTICLE
Dysregulated Cell Signaling Pathways in Prostate Tumoral Plasticity—Checkpoints
Elena Matei1,*, Ionuț Ciprian Iorga2,3, Mariana Deacu2,4, Georgeta Camelia Cozaru1,4, Gabriela Isabela Băltățescu1,4,#, Manuela Enciu2,4,#
1 Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, “Ovidius” University of Constanta, 145 Tomis Blvd., Constanta, Romania
2 Medicine Faculty, “Ovidius” University of Constanta, 1 Universitatii Street, Constanta, Romania
3 Urology Department, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., Constanta, Romania
4 Clinical Service of Pathology, “Sf. Apostol Andrei” Emergency County Hospital, 145 Tomis Blvd., Constanta, Romania
* Corresponding Author: Elena Matei. Email: 
# These authors contributed equally to this work
Oncology Research https://doi.org/10.32604/or.2026.072421
Received 26 August 2025; Accepted 02 February 2026; Published online 26 March 2026
Abstract
Objectives: 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. Methods: 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). Results: In our study, in benign prostatic hyperplasia (BPH) tissue samples, the low S-proliferative phase category of the cell cycle (SH: <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, >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. Conclusion: 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.
Keywords
Epithelial-mesenchymal transition (EMT); necrosis-apoptosis continuum; DNA damage; transcription factor p53; autophagy; microenvironment
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