The transcription factor basonuclin-1, a new player in the progression of triple-negative inflammatory breast cancer

We aim to understand the pathogenesis of Inflammatory Breast Cancer (IBC), the deadliest breast cancer type with a 5-year survival of ~34%. IBC is an aggressive, poorly understood form of breast cancer, known for tumor emboli formation. While progress has been made in HER2+ and hormonal receptor-positive IBC, the prognosis for triple-negative (ER-/PR-/HER2-) IBC remains grim. Aberrant transcriptional regulation is a common feature in cancer. There is still a gap in understanding the molecular signature of IBC, and in identifying genes or pathways involved in its aggressive metastatic phenotype. IBC is characterized by the formation of intralymphatic tumor emboli that may contribute to metastasis, but the molecular mechanism is poorly understood. We analyzed RNAseq data, revealing differentially expressed transcription factor genes in IBC. Notably, the triple-negative IBC cell line, SUM149PT, consistently displayed high basonuclin-1 (BNC-1) expression. BNC-1 is a zinc finger transcription factor linked to epithelial expansion, and brain metastasis in breast cancer. Its role in IBC, particularly triple-negative IBCs, remains unexplored. This proposal tests the hypothesis that BCN-1 has a role in the pathogenesis of IBC as an oncogene by contributing the development of oncogenic phenotypes including tumor emboli coupled with metastasis. Our proposed study will allow us to: (1) investigate how BNC-1 promotes oncogenic phenotypes, which leads to the progression of IBC and elucidate changes associated with IBC metastasis using 3D cell culture model that mimics the tumor microenvironment, and (2) to identify novel genes or pathways involved in the pathogenesis of IBC that could be used for the design of novel therapeutic strategies. Our overarching hypothesis is that BCN-1 has a role in the pathogenesis of IBC as an oncogene by contributing to the development of oncogenic phenotypes coupled with metastasis. Our research sheds light on the molecular landscape of IBC, potentially paving the way for targeted therapies, and identification of biomarkers. The innovation of this study is the use of an integrative approach by combining an innovative 3D culture model, and omics technologies to characterize molecular and cellular changes associated with BNC-1 in IBC. This will also lead to the potential validation of BNC-1 as a novel biomarker for diagnosis, prognosis, and/or targeted therapy option for IBC patients. These SuRE project objectives will greatly enrich research excellence and capacity at UPR-RP by fostering collaboration and providing high-quality research opportunities for promising students aspiring to become future scientific leaders.