Biology subjects

Eryilmaz, E.

Publications and source records attributed to Eryilmaz, E..

2 recordsLinked to original sources

bioRxiv2026

Vegfc-Vegfr3-Dependent Lymphatic Sprouting Requires Apelin Signaling

While Vegfc-Vegfr3 signaling is the primary driver of lymphangiogenesis, the role of G protein-coupled receptors (GPCRs), the most successful class of druggable targets in the human genome, remains far less understood. A previous study has implicated Apelin signaling and its receptor Apelin receptor (Aplnr), a class A GPCR, in lymphatic development, yet the underlying cellular and molecular mechanisms remain unclear. Here, we show that Apelin signaling is indispensable for Vegfc-Vegfr3-dependent lymphatic sprouting and promotes lymphatic endothelial cell (LEC) migration without affecting LEC specification. Loss of Apelin signaling resulted in defective sprouting of ECs from the posterior cardinal vein (PCV) and subsequent failure of lymphatic vessel formation. Conversely, Apelin overexpression induces ectopic endothelial extensions from the PCV, an effect that is suppressed by reducing Vegfr3 signaling. Mechanistically, we show that Vegfc signaling through ERK activation regulates Aplnr expression. We propose that the specific upregulation of Aplnrb in LECs renders them migration-competent, establishing Apelin signaling as a critical and non-redundant regulator of lymphatic sprouting. Overall, our results reveal a tightly coordinated signaling axis between growth factor and GPCR pathways that governs lymphatic endothelial behavior.

developmental biology↗

bioRxiv2026

Proximity-Informed Graph Learning Defines Spatial Protein Communities for Tumor-Associated Proximity Antigen Discovery

The spatial organization of membrane proteins is an underexplored dimension of cell-surface biology. Spatial proximity shapes cellular function and therapeutic targetability, yet efforts to identify tumor-associated antigens (TAAs) have largely focused on expression alone. Here, we developed an industrialized surface-protein proximity mapping workflow to interrogate TAAs within their membrane microenvironments. In the process, we generated 248 proximity maps across 12 receptor tyrosine kinases (RTKs) and 28 tumor cell systems. This proximity atlas enabled two advances: first, MetaMap, a correlation-based analytical framework that defines spatial protein communities and infers non-targeted proximal proteins from reproducible proximity signatures; and second, tumor-associated proximity antigens (TAPAs), a conceptual class of co-targets defined by disease-specific spatial proximity to TAAs rather than expression alone. Applying these proximity-derived relationships within a multimodal prioritization framework, we identified and validated an EGFRxCDCP1 TAA-TAPA pair that enhanced tumor cell killing across therapeutic modalities. By integrating spatial organization with multimodal data, this work expands the design space for precision-guided therapeutic strategies.

cancer biology↗