Related Experiment Video
Updated: Sep 17, 2025
Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival
Haruka Kurosu1,2, Norika Yamada2, Ritsuko Nakamura2
1Department of Urology, Aichi Medical University School of Medicine, Japan.
Abstract:
The facilitates chromatin transcription (FACT) complex is composed of SSRP1 and SUPT16H subunits and participates in nucleosomal reorganization; hence, FACT inhibitors are considered promising therapeutics for malignant tumors. Here, we show that adipocyte enhancer binding protein 1 (AEBP1) attenuates the dependency of bladder cancer cell survival on the FACT complex via the expression of GLI1, a pivotal transcription factor in Hedgehog signaling. In AEBP1-high expressing bladder cancer cell lines, AEBP1 knockdown inhibited cellular proliferation and induced the marker expression of apoptosis and DNA damage/replication stress. RNA-sequencing revealed that AEBP1 knockdown suppressed the expression of SSRP1 and SUPT16H; however, the knockdown of both subunits was less effective than AEBP1 knockdown in inducing apoptosis or DNA damage markers in AEBP1-high expressing cells. AEBP1 knockdown reduced the protein levels of GLI1, and treatment with the GLI-specific inhibitor GANT61 induced markers that were not suppressed by the forced expression of AEBP1. These findings suggest that AEBP1-mediated GLI1 expression reduces the FACT complex dependency of bladder cancer cell survival.
Insights
Adipocyte enhancer binding protein 1 (AEBP1) helps bladder cancer cells survive by regulating GLI1 and the FACT complex. AEBP1 knockdown inhibits cancer cell growth and increases apoptosis, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The facilitates chromatin transcription (FACT) complex is crucial for nucleosomal reorganization and is a target for cancer therapeutics.
- Bladder cancer cell survival is often linked to specific molecular pathways.
Purpose of the Study:
- To investigate the role of adipocyte enhancer binding protein 1 (AEBP1) in bladder cancer cell survival.
- To elucidate the mechanism by which AEBP1 influences dependency on the FACT complex.
Main Methods:
- Utilized bladder cancer cell lines with varying AEBP1 expression levels.
- Performed AEBP1 knockdown and analyzed effects on proliferation, apoptosis, and DNA damage markers.
- Conducted RNA-sequencing to assess gene expression changes.
- Investigated GLI1 protein levels and utilized a GLI-specific inhibitor (GANT61).
Main Results:
- AEBP1 knockdown in high-expressing bladder cancer cells inhibited proliferation and induced apoptosis and DNA damage markers.
- RNA-sequencing showed suppressed expression of FACT complex subunits (SSRP1, SUPT16H) upon AEBP1 knockdown.
- AEBP1 knockdown reduced GLI1 protein levels, and GLI inhibition mimicked some effects of AEBP1 knockdown.
Conclusions:
- AEBP1 promotes bladder cancer cell survival by upregulating GLI1, which in turn reduces the cancer cells' reliance on the FACT complex.
- Targeting AEBP1 or the GLI1 pathway presents a potential therapeutic strategy for bladder cancer.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
02:23Abnormal Proliferation
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:23Negative Regulator Molecules
02:38Mitogens and the Cell Cycle
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...