Work

RBBP5 drives cancer stem cell-like characteristics by suppressing the hippo signaling pathway through WNT5A downregulation in breast cancer

Year: 2026

Type: article

Abstract: BACKGROUND: Cancer stem cells (CSCs) are a major contributor to breast cancer recurrence and therapeutic resistance. This study investigates the oncogenic role of Retinoblastoma Binding Protein 5 (RBBP5) in driving CSC-like properties in breast cancer. METHODS: Genetic alterations in RBBP5 and their correlation with patient survival were analyzed using multiple breast cancer cohorts, including METABRIC, TCGA, and Kaplan-Meier (KM) plotter datasets. The impact of RBBP5 on CSC-like traits was assessed through tumorsphere formation and ALDEFLUOR assays, and in vivo xenograft models. To elucidate the underlying molecular mechanism, RNA sequencing (RNA-seq) was performed. RESULTS: < 0.001). RBBP5 overexpression enhanced tumorsphere-forming capacity, CSC-like population and tumor-initiating cell frequency. RNA-seq results revealed an enrichment of gene sets associated with negative regulation of cell growth, invasiveness, and stem cell population in RBBP5-knockdown cells. RBBP5 knockdown upregulated WNT5A, a non-canonical Wnt ligand, leading to Hippo pathway activation and subsequent suppression of YAP signaling. Pharmacological inhibition of YAP1 abrogated RBBP5-induced CSC-like properties, while suppression of MST1/2 in RBBP5-knockdown cells restored YAP activity and CSC traits. CONCLUSIONS: These findings indicate that RBBP5 promotes CSC-like properties in breast cancer by repressing WNT5A-mediated Hippo signaling. We suggest RBBP5 as a potential biomarker for poor prognosis and propose that targeting YAP or activating the Hippo pathway could represent a promising therapeutic approach for patients with RBBP5-overexpressing tumors.

Source: Cancer Biology & Therapy

DOI: 10.1080/15384047.2026.2756150

Authors: So-Jeong Moon, Young-Hyeon Kye, Gu Kong

Institution: Hanyang University

Language: English

Topic: Hippo pathway signaling and YAP/TAZ

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,970