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.

SOX9 is upregulated in the majority of pancreatic ductal adenocarcinoma cases. It is hypothesized that the increased expression of SOX9 is necessary for the formation and maintenance of tumor phenotypes in pancreatic cancer cells. In our research, we studied six pancreatic cancer cell lines, which displayed varying levels of differentiation and a range of oncogenic mutations. We chose the method of downregulation of SOX9 expression via siRNA transfection as the main method for investigating the functional role of the SOX9 factor in pancreatic cancer cells. We discovered that the downregulation of SOX9 expression in the cell lines leads to cell-line-specific changes in the expression levels of epithelial and mesenchymal protein markers. Additionally, the downregulation of SOX9 expression had a specific effect on the expression of pancreatic developmental master genes. SOX9 downregulation had the greatest effect on the expression levels of the protein regulators of cell proliferation. In three of the four cell lines studied, the transfection of siSOX9 led to a significant decrease in proliferative activity and to the activation of proapoptotic caspases in transfected cells. The acquired results demonstrate that the SOX9 protein exerts its multiple functions as a pleiotropic regulator of differentiation and a potential promoter of tumor growth in a cell-specific manner in pancreatic cancer cells.

SOX9 is widely regarded as a key master regulator of gene transcription, responsible for the development and differentiation programs within tissue and organogenesis, particularly in the pancreas. SOX9 overexpression has been observed in multiple tumor types, including pancreatic cancer, and is discussed as a prognostic marker. In order to gain a more profound understanding of the role of SOX9 in pancreatic cancer, we have performed SOX9 knockdown in the COLO357 and PANC-1 cells using RNA interference, followed by full-transcriptome analysis of the siRNA-transfected cells. The molecular pathway enrichment analysis between SOX9-specific siRNA-transfected cells and control cells reveals the activation of processes associated with cellular signaling, cell differentiation, transcription, and methylation, alongside the suppression of genes involved in various stages of the cell cycle and apoptosis, upon the SOX9 knockdown. Alterations of the expression of transcription factors, epithelial–mesenchymal transition markers, oncogenes, tumor suppressor genes, and drug resistance-related genes upon SOX9 knockdown in comparison of primary and metastatic pancreatic cancer cells are discovered. The expression levels of genes comprising prognostic signatures for pancreatic cancer were also evaluated following SOX9 knockdown. Additional studies are needed to assess the properties and prognostic significance of SOX9 in pancreatic cancer using other biological models.