👤 Hyewhon Rhim

Pancreatic ductal adenocarcinoma (PDAC) is therapeutically recalcitrant and metastatic. Partial epithelial to mesenchymal transition (EMT) is associated with metastasis; however, a causal connection needs further unraveling. Here, we use single-cell RNA sequencing and genetic mouse models to identify the functional roles of partial EMT and epithelial stabilization in PDAC growth and metastasis. A global EMT expression signature identifies ∼50 cancer cell clusters spanning the epithelial-mesenchymal continuum in both human and murine PDACs. The combined genetic suppression of Snail and Twist results in PDAC epithelial stabilization and increased liver metastasis. Genetic deletion of Zeb1 in PDAC cells also leads to liver metastasis associated with cancer cell epithelial stabilization. We demonstrate that epithelial stabilization leads to the enhanced collective migration of cancer cells and modulation of the immune microenvironment, which likely contribute to efficient liver colonization. Our study provides insights into the diverse mechanisms of metastasis in pancreatic cancer and potential therapeutic targets. Show less

The gene expression profiles of lysophosphatidic acid (LPA)-treated young and senescent human diploid fibroblasts (HDFs) were examined using cDNA microarray analysis. The expression of some genes, including EGR 1/3 and MRRF, was controlled by LPA similarly in young and senescent cells, showing a typical time-dependent up-and-down expression profile. In contrast, some other genes, including DUSP6, CYR61, and F3, showed sustained upregulation in senescent HDFs later after LPA treatment. These genes might be involved in altered LPA responsiveness during the aging process. Show less