PUBLICATION
TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system
- Authors
- Bochen, F., Subedi, S., La Manna, F., Jarrin, S., Papapostolou, I., Kruithof-de Julio, M., Peinelt, C.
- ID
- ZDB-PUB-250118-1
- Date
- 2025
- Source
- Molecular Oncology : (Journal)
- Registered Authors
- Keywords
- TRPM4, cell death, ion channel, prostate cancer, tumor spheroid, zebrafish
- MeSH Terms
-
- Cell Death
- Male
- Prostatic Neoplasms*/genetics
- Prostatic Neoplasms*/metabolism
- Prostatic Neoplasms*/pathology
- Xenograft Model Antitumor Assays
- Zebrafish
- Spheroids, Cellular*/metabolism
- Spheroids, Cellular*/pathology
- Cell Proliferation
- Animals
- Humans
- Gene Expression Regulation, Neoplastic
- Neoplasm Metastasis
- TRPM Cation Channels*/genetics
- TRPM Cation Channels*/metabolism
- Cell Line, Tumor
- PubMed
- 39821469 Full text @ Mol. Oncol.
Citation
Bochen, F., Subedi, S., La Manna, F., Jarrin, S., Papapostolou, I., Kruithof-de Julio, M., Peinelt, C. (2025) TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system. Molecular Oncology. :.
Abstract
Transient receptor potential melastatin-4 (TRPM4) ion channel expression is upregulated in prostate cancer (PCa), contributing to increased cell proliferation, migration, adhesion, epithelial-to-mesenchymal transition, cell cycle shift, and alterations of intracellular Ca2+ signaling. GEO2R platform analysis of messenger RNA (mRNA) expression of ~ 6350 genes in normal and malignant prostate tissue samples from 15 PCa patients demonstrates that TRPM4 expression is upregulated sixfold and is among the most significantly upregulated genes in PCa. We find that absence of TRPM4 reduced PCa tumor spheroid size and decreased PCa tumor spheroid outgrowth. In addition, lack of TRPM4 increased cell death in PCa tumor spheroids, a phenotype that is absent in two-dimensional (2D) cancer cell systems. Lastly, absence of TRPM4 in PCa cells reduced extravasation and metastatic burden in a preclinical zebrafish cancer model. Taken together, our findings show that TRPM4 is an attractive therapeutic target in PCa and highlights the need for future development of pharmacological tools.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping