Abstract 1460: Clinical relevance of a super-enhancer-associated actin polymerization promoting-factor in endometrial cancer

Abstract Super-enhancers (SEs) are defined as large clusters of enhancers regulating transcription of genes that exhibit cell-type specific functions. SEs in cancers are often different from those in healthy states and responsible for the development and progression of the disease. We here study the clinical role of a super-enhancer-associated actin polymerization promoting-factor, cordon-bleu WH2 repeat protein-like 1 (COBLL1), in endometrial cancer, since we previously demonstrated its tumor-promoting role in castration-resistant prostate cancer [Proc Natl Acad Sci USA 115:4975, 2018]. In the present study, using multiple patient-derived spheroid cultures established by our group [Endocrinology 160:1895, 2029], endometrial cancer-specific SEs were identified by chromatin immunoprecipitation (ChIP) sequencing for H3K27ac binding sites. Among top-ranked SE-associated genes, we focused on the relevance of COBLL1 in endometrial cancer. Then, we showed that COBLL1 silencing in endometrial cancer cells substantially repressed cell proliferation and reduced the populations of cells in S phase of the cell cycle. Of note, immunohistochemical study of clinical endometrial cancer tissues revealed that COBLL1 immunoreactivity was well correlated with poor prognosis of the patients. Our findings suggest that COBLL1 plays a relevant role in the pathophysiology of endometrial cancer and can be applied as a promising diagnostic and therapeutic target in endometrial cancer management. Citation Format: Kuniko Horie, Erina Iwabuchi, Kazuhiro Ikeda, Takashi Suzuki, Satoshi Inoue. Clinical relevance of a super-enhancer-associated actin polymerization promoting-factor in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1460.