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Updated: May 25, 2025

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
BIN1 inhibited tumor growth, metastasis and stemness by ALDH1/NOTCH pathway in bladder carcinoma
Si-Yu Chen1,2, Ya-Long Zhang1,2, Xiao-Ran Li1,2
1Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.
Background:
Bladder cancer (BLCA) represents one of the most prevalent urological malignancies worldwide. Bridging integrator 1 (BIN1), a well-characterized tumor suppressor that interacts with and inhibits oncogenic Myc transcription factors, has demonstrated crucial roles in various cancer types. However, its specific functions and underlying molecular mechanisms in BLCA development and progression remain poorly understood. This study aims to elucidate the role of BIN1 in regulating BLCA cell proliferation, metastasis, and cancer stem cell properties.
Methods:
Using urinary proteomics analysis, we identified BIN1 as a significantly dysregulated protein in BLCA. The clinical significance of BIN1 was further validated through comprehensive analyses of public databases. BIN1 expression levels defined distinct molecular and immunological subtypes of BLCA. Through proteomic profiling of BIN1-overexpressing UMUC3 cells and corresponding controls, we identified ALDH1 as a key downstream effector in the BIN1-regulated ALDH1/NOTCH signaling axis. We employed multiple experimental approaches, including Western blot analysis, quantitative RT-PCR, immunofluorescence staining, wound healing assays, transwell migration assays, colony formation assays, tumor sphere formation assays, flow cytometry, CCK8 proliferation assays, and cell transfection experiments.
Results:
We observed significant downregulation of BIN1 in both BLCA tissues and cell lines compared to normal adjacent tissues and SV-HUC-1 cells, respectively. BIN1 overexpression inhibited cancer cell proliferation by promoting apoptosis and suppressed epithelial-mesenchymal transition (EMT), thereby reducing local invasion and distant metastasis. Additionally, BIN1 regulated cancer stem cell properties through modulation of ALDH1 expression, with NOTCH2 acting as a crucial downstream mediator of ALDH1 signaling.
Conclusion:
Our findings demonstrate that BIN1 functions as a tumor suppressor in BLCA and suggest its potential utility as both a diagnostic biomarker and therapeutic target for BLCA treatment.
Insights
Bridging integrator 1 (BIN1) acts as a tumor suppressor in bladder cancer (BLCA), inhibiting proliferation and metastasis. BIN1 downregulation is observed in BLCA, suggesting its potential as a diagnostic biomarker and therapeutic target.
Area of Science:
- Urology
- Oncology
- Molecular Biology
Background:
- Bladder cancer (BLCA) is a prevalent urological malignancy.
- Bridging integrator 1 (BIN1) is a known tumor suppressor with poorly understood roles in BLCA.
- This study investigates BIN1's function in BLCA development and progression.
Purpose of the Study:
- To elucidate the role of BIN1 in regulating BLCA cell proliferation, metastasis, and cancer stem cell properties.
- To identify BIN1 as a potential diagnostic biomarker and therapeutic target for BLCA.
Main Methods:
- Urinary proteomics and public database analysis identified BIN1 dysregulation in BLCA.
- Proteomic profiling revealed ALDH1 as a downstream effector in the BIN1-regulated ALDH1/NOTCH signaling axis.
- Experimental validation included Western blot, RT-PCR, immunofluorescence, migration, proliferation, and cell transfection assays.
Main Results:
- BIN1 was significantly downregulated in BLCA tissues and cell lines.
- BIN1 overexpression inhibited proliferation, promoted apoptosis, and suppressed epithelial-mesenchymal transition (EMT), reducing metastasis.
- BIN1 modulated cancer stem cell properties via ALDH1 and NOTCH2 signaling.
Conclusions:
- BIN1 functions as a tumor suppressor in bladder cancer.
- BIN1 holds potential as a diagnostic biomarker and therapeutic target for BLCA treatment.
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