Investigating the function of HuR in murine PDAC tumors via single-cell sequencing

The role of tumor-intrinsic post-transcriptional gene regulation in driving tumor-immune crosstalk has been relatively unexplored. Here, we report that the RNA-binding protein, HuR (ELAVL1), is enriched in human PDAC and that genetic disruption of HuR impaired tumor growth.

Comprehensive spatial and flow cytometry profiling of the PDAC TME revealed that genetic disruption of HuR in PDAC enhanced both T cell number and functional state. Mechanistically, single-cell RNA sequencing in vivo showed that HuR stabilizes mTOR pathway transcripts critical for metabolic adaptation in PDAC. HuR-driven metabolic reprogramming promotes tumor nutrient dominance and limits nutrient consumption by neighboring tumor-reactive T cells.