BAP31 Promotes Angiogenesis via Galectin-3 Upregulation in Neuroblastoma.

Neuroblastoma (NB) is one of the highly vascularized childhood solid tumors, and understanding the molecular mechanisms underlying angiogenesis in NB is crucial for developing effective therapeutic strategies. B-cell receptor-associated protein 31 (BAP31) has been implicated in tumor progression, but its role in angiogenesis remains unexplored. This study investigated BAP31 modulation of pro-angiogenic factors in SH-SY5Y NB cells. Through protein overexpression, knockdown, antibody blocking, and quantification experiments, we demonstrated that overexpression of BAP31 led to increased levels of vascular endothelial growth factor A (VEGFA) and Galectin-3 (GAL-3), which are known to promote angiogenesis. Conditioned medium derived from BAP31-overexpressing neuroblastoma cells stimulated migration and tube formation in endothelial cells, indicating its pro-angiogenic properties. Also, we demonstrated that BAP31 enhances capillary tube formation by regulating hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target, GAL-3. Furthermore, GAL-3 downstream proteins, Jagged 1 and VEGF receptor 2 (VEGFR2), were up-regulated, and blocking GAL-3 partially inhibited the BAP31-induced tube formation. These findings suggest that BAP31 promotes angiogenesis in NB by modulating GAL-3 and VEGF signaling, thereby shaping the tumor microenvironment. This study provides novel insights into the pro-angiogenic role of BAP31 in NB.

Biological roles of the B cell receptor-associated protein 31: Functional Implication in Cancer.

BAP31 is a ubiquitously expressed integral membrane protein of the endoplasmic reticulum. BAP31 is involved in various biological and molecular processes, including protein transport, viral processing, apoptosis signaling, MHC 1 antigen processing and presentation, mitochondria and ER calcium regulation, and proteasomal protein degradation. We employed a BAP31 interaction search using STRING and inBioMap™ protein-protein interaction networks, and the Metabolic Atlas, which revealed molecular and metabolic interactors involved in various pathways essential for cell growth, cell survival, and disease development. BAP31, as a chaperone and resident protein of the ER, was reported in the development of some central nervous system disorders and metabolic diseases about AD, ALS, and Liver disease. In addition, BAP31 is overexpressed in many cancers. Furthermore, research around BAP31 involvement in cancer has taken up a shape, focusing on its roles in cancer cell survival, disease prognosis, and targeted treatment. Here, we address published data on the Biological roles of BAP31 in both health and disease. We present an analytical description of BAP31 expression and functional implication in some human cancers and the impact of its expression and regulation while it models as a potential target in cancer therapy. Besides, a profound understanding of BAP31 is insightful of the gap between cancer development and neurodegeneration, thus generating novel ideas surrounding the link between the two different cell phenomena.

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation.

B-cell receptor-associated protein 31 (BAP31) is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein that has been found to be overexpressed in gastric intestinal-type adenocarcinoma. We first studied the relationship of BAP31 with 84 kinds of tumor-associated antigens and found that BAP31 can specifically interact with and regulate the proteasome degradation of the cyclin kinase inhibitor p27kip1 , which is one of the most frequently dysregulated tumor suppressor proteins in human cancers. Therefore, we screened antibodies against BAP31 from a human VH single-domain antibody library and expressed the antibodies intracellularly. It was found that one of the intrabodies (VH-D1) specifically inhibited p27kip1 proteasome degradation, possibly by blocking the combination of BAP31 with p27kip1 . VH-D1 displayed therapeutic effects, as it was able to reduce the growth of human gastric cancer (GC) cell xenografts in nude mice. This effect was due to inhibition of the proliferation and subsequent activation of caspase-dependent apoptosis. Thus, BAP31 is a potential target for the suppression of GC via an intrabody-based approach.