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Published on: March 29, 2019
Reprogramming-driven Proteomic Shifts Mirror Bladder Cancer Progression and Reveal Biomarker Candidates Across
Banu Iskender1, Mehmet Sarihan2, Bengi Su Rumeysa Barlak2
1Protein Research and Proteomics Laboratory, Department of Medical Biology, Faculty of Medicine, Kocaeli University, Izmit, Türkiye banu.iskender@kocaeli.edu.tr banu.iskender@yahoo.com.
Cancer Genomics & Proteomics
|June 29, 2026
Summary
Bladder cancer progression involves stem-like cells and plasticity. This study reveals grade-specific signaling changes during cell reprogramming and differentiation, offering new therapeutic targets and biomarkers for bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor progression and therapeutic resistance in bladder cancer are linked to stem-like properties and cellular plasticity.
- Molecular changes driving these traits across different bladder cancer grades are not well understood.
- This study investigates signaling networks and proteomic landscapes during bladder cancer cell reprogramming.
Purpose of the Study:
- To examine dynamic signaling network and proteomic landscape rewiring during the reprogramming of low-grade (HTB-2) and high-grade (HTB-5) bladder cancer cells.
- To analyze subsequent differentiation into embryoid bodies to understand grade-specific molecular trajectories.
- To identify plasticity-associated signatures and their clinical relevance in bladder cancer.
Main Methods:
- Analyzed six experimental models: parental (HTB-2, HTB-5), reprogrammed (rep HTB-2, rep HTB-5), and embryoid bodies (rep HTB-2 EB, rep HTB-5 EB), with SV-HUC-1 uroepithelial cells as control.
- Performed phosphoproteomic and integrated proteomic analyses to define signaling architectures and plasticity signatures.
- Validated findings using pan-cancer datasets.
Main Results:
- Phosphoproteomics revealed grade-dependent kinase networks; HTB-2 cells showed enhanced MAPK/Src signaling, while HTB-5 cells displayed increased AKT/STAT signaling and reduced ERK signaling.
- Differentiation led to metabolic reprogramming in low-grade cells and cytoskeletal/ECM remodeling in high-grade cells.
- Integrated proteomics identified a shared plasticity signature, with reprogrammed models reflecting key bladder cancer features and outcomes.
Conclusions:
- Reprogramming induces a transient state enabling invasive features upon re-differentiation, supporting a hierarchical bladder cancer progression model.
- Grade-specific signaling and proteomic adaptations highlight differentiation as a key window for biomarkers and therapeutic targets.
- Reprogrammed bladder cancer models offer a relevant platform for studying tumor plasticity, progression, and therapeutic vulnerabilities.
