Dynamic translocation of Inside-Out proteins to the cell surface underlies cellular adaptation to cancer-induced stress - PubMed
8 hours ago
- #stress response
- #cancer biology
- #protein trafficking
- Inside-Out (I-O) protein display refers to the noncanonical surface localization of intracellular proteins on cancer cells, which is an underexplored aspect of tumor biology.
- Using APEX2-mediated proximity biotinylation and a custom antibody platform, researchers identified about 140 high-confidence I-O proteins, enriched in stress-response pathways like ribosomal, proteasomal, chaperone, and translation factors.
- Validation across seven tumor cell lines confirmed selective surface localization, with in vivo imaging showing tumor-specific antibody accumulation in mouse xenografts, and absence on normal cells like PBMCs.
- I-O protein tethering to the membrane depends on heparan sulfate interactions; their removal clears proteins from the surface, but levels return within 6 hours, indicating dynamic ER-Golgi trafficking linked to cellular stress.
- Nearly half of I-O proteins overlap with stress granule components, but stress factors promoting SG formation do not similarly affect I-O display, suggesting parallel, mechanistically distinct stress responses.