Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells

SIMPLE SUMMARY: A possible way to inhibit tumor cells migration could be strengthening adhesion between tumor and stromal cells in primary solid tumors. Expanding on our previous findings, we have shown that ectopic expression of the pancreatic lineage specifier PDX1 reduces the migration potential of pancreatic cancer cells by increasing their adhesiveness and reducing the sensitivity to TGFβ1-induced epithelial-mesenchymal transition. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Our study highlights a potential window for the PDX1 therapeutic application as an antimetastatic agent at the initial stages of cancer development. ABSTRACT: Intercellular interactions involving adhesion factors are key operators in cancer progression. In particular, these factors are responsible for facilitating cell migration and metastasis. Strengthening of adhesion between tumor cells and surrounding cells or extracellular matrix (ECM), may provide a way to inhibit tumor cell migration. Recently, we demonstrated that PDX1 ectopic expression results in the reduction of pancreatic cancer line PANC-1 cell motility in vitro and in vivo, and we now provide experimental data confirming the hypothesis that suppression of migration may be related to the effect of PDX1 on cell adhesion. Cell migration analyses demonstrated decreased motility of pancreatic Colo357 and PANC-1 cell lines expressing PDX1. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Expression of the EMT regulator genes was only mildly induced in cells expressing PDX1 during the simulation of the epithelial-mesenchymal transition (EMT) by the addition of TGFβ1 to the medium. PDX1-expressing cancer cell lines showed increased cell adhesion to collagen type I, fibronectin, and poly-lysine. We conclude that ectopic expression of PDX1 reduces the migration potential of cancer cells, by increasing the adhesive properties of cells and reducing the sensitivity to TGFβ1-induced EMT.