Open Access

ARTICLE

Dysregulated Cell Signaling Pathways in Prostate Tumoral Plasticity—Checkpoints

Elena Matei^1,*, Ionuț Ciprian Iorga^2,3, Mariana Deacu^2,4, Georgeta Camelia Cozaru^1,4, Gabriela Isabela Băltățescu^1,4,#, Manuela Enciu^2,4,#

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

(This article belongs to the Special Issue: Emerging Insights into the Tumor Microenvironment: Mechanisms, Therapeutic Targets, and Clinical Applications)

Oncology Research 2026, 34(6), 16 https://doi.org/10.32604/or.2026.072421

Received 26 August 2025; Accepted 02 February 2026; Issue published 21 May 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.

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Supplementary Material

Supplementary Material File

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