Spatiotemporal Decoding of Tumor Contactome Unveils a Microbial-Sensitive Ctrb1-Dependent Cell Competition Architecture Driving Epithelial-Mesenchymal Defense Against Cancer

While non-immune epithelial surveillance constitutes a crucial frontline defense against early tumorigenesis, its operational mechanisms - particularly the cellular components and structural basis of cell competition - remain poorly defined. In this study, we uncover a novel cell competition architecture which we termed as proliferative containment layer (PCL), comprising coordinated epithelial-mesenchymal cell assemblies. Employing our newly developed Surface-anchored TurboID-mediated Contact-dependent Labeling (STCL) system, we achieved in situ biotinylation of membrane proteins on interacting cells, enabling the first dynamic mapping of direct tumor-stromal interactomes in a tumor-suppressive competition model. Mechanistically, direct tumor cell contact triggers a unique epithelial-mesenchymal defense against cancer (EMDAC) program, where PCL components acquire superior proliferative capacity through chymotrypsinogen B1 (CTRB1)-mediated coordination of Myc/YAP signaling axes. Notably, we demonstrate that CTRB1 serves as a molecular rheostat integrating multiple proliferation pathways to establish competitive dominance, while microbial infection unexpectedly suppresses CTRB1 expression and compromises tumor clearance. This work fundamentally advances our understanding of non-immune surveillance by: 1) Identifying PCL as a spatially organized defense unit; 2) Deciphering EMDAC as a dual-lineage competition mechanism; 3) Establishing CTRB1 as a microbial-sensitive master regulator of cellular fitness during competition.