AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival

Haruka Kurosu; Norika Yamada; Ritsuko Nakamura; Hideaki Ito; Koji Ohnishi; Akihito Inoko; Miho Riku; Tomoaki Muramatsu; Naoto Sassa; Kenji Kasai

doi:10.1016/j.bbrep.2025.102101

AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival

Biochem Biophys Rep. 2025 Jun 20:43:102101. doi: 10.1016/j.bbrep.2025.102101. eCollection 2025 Sep.

Authors

Affiliations

¹ Department of Urology, Aichi Medical University School of Medicine, Japan.
² Department of Pathology, 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.

Keywords: AEBP1; Apoptosis; Bladder cancer; DNA damage; FACT complex; GLI1.