Selected Grantee Publications

Pancreatic Cancer Cells Upregulate LPAR4 in Response to Isolation Stress to Promote an ECM-Enriched Niche and Support Tumour Initiation

Wu et al., Nature Cell Biology. 2023.

https://pubmed.ncbi.nlm.nih.gov/36646789/

Understanding drivers of tumor initiation is critical for cancer therapy. Investigators found transient increase of lysophosphatidic acid receptor 4 (LPAR4) in pancreatic cancer cells exposed to environmental stress or chemotherapy. LPAR4 induced tumor initiation, stress tolerance, and drug resistance by downregulating miR-139-5p, a tumor suppressor, and upregulating fibronectin. These results indicate that LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix (ECM), allowing cells to survive isolation stress and compensate for the absence of stromal-derived factors by creating their own tumor-initiating niche. Supported by ORIP (K01OD030513, T32OD017863), NCI, and NHLBI.