Journal Article Ppublish
PubMed: 40064277 DOI: 10.1016/j.ijbiomac.2025.141915
Upstream-binding protein-1 promotes breast tumorigenesis by inducing NRG2-mediated metastasis, plasticity, and macrophage polarization.
Int J Biol Macromol 307(Pt 2):141915
Authors: Apurva Jaiswal, Manorma Negi, Eun Ha Choi, Nagendra Kumar Kaushik, Neha Kaushik
Affiliations
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea.
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea.
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea.
- Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong 18323, Republic of Korea.
Abstract
Upstream binding protein 1 (UBP1) is a transcription factor (TF) of the CP2/grainyhead family involved in various biological processes, including cancer cell proliferation, differentiation, and embryonic development. While other mammalian grainyhead-like TFs have been linked to different cancers, including breast cancer (BC), the role of UBP1 in BC remains unexplored. In this study, we provide a preliminary investigation into the novel functions of UBP1 in BC. Using online database screening, we first demonstrated that elevated UBP1 levels in breast carcinoma are associated with poor prognosis and adverse clinical outcomes. We further showed that UBP1 promotes epithelial-mesenchymal transition (EMT) and stemness in BC cells while regulating key signaling pathways, including the PI3K-Akt. Additionally, UBP1 modulates tumor metastasis by influencing tumor-associated macrophage (TAM) polarization, promoting an immunosuppressive macrophage phenotype, and driving tumor progression. Our findings highlight UBP1's pivotal role in BC progression through multiple mechanisms, including EMT induction, stemness maintenance, and macrophage polarization via activation of the NRG2/Akt axis. Moreover, higher UBP1 expression correlates with lower overall and recurrence-free survival, underscoring its potential as a prognostic marker and therapeutic target for aggressive BC.
MeSH
Cells, Breast Neoplasms, Macrophages, Neoplasms, Neoplasm Metastasis, Breast, Carcinogenesis