Pancreatic cancer cells upregulation of LPA receptor 4 in response to stress create a tumor-initiating niche

We report that the lysophosphatidic acid receptor 4 (LPAR4) is specifically upregulated on cells exposed to environmental stress or cancer drugs where it promotes stress tolerance, self-renewal, and tumor initiation. We find that ectopic LPAR4-expressing tumors display an enrichment of key extracellular matrix (ECM)-related genes that are established drivers of cancer stemness, and surprisingly do not require stimulation with the canonical LPAR4 ligand, LPA. From this RNAseq data, we observed that LPAR4 promotes a subset of genes, mainly extracellular matrix related genes, independent of its ligand LPA in patient-derived xenograft cells. 79E+EV vs. 79E+LPAR4 cells, treated with or without 1 µM LPA for 2 hours. Each group has 3 replicates, there are 12 samples in total. 79E+EV without LPA stimulation was the control group.