TBX3 enhances invasivness in PDAC

Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators during early embryonic development. Intriguingly, those developmental pathways frequently become reactivated during cancer formation. Recently, we could show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro. Forced TBX3 expression in murine ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling (Weidgang, Stem Cell Reports, 2013).

The role of TBX3 in different cancer types has been shown to be tissue-specific. However to date, its in during pancreatic cancer remains enigmatic. Herein, we aim to delineate TBX3 function in pancreatic cancer. We found that overexpression of TBX3 enhanced the invasive and migratory potential of several pancreatic ductal carcinoma cell lines, while the proliferative capacity remained unaffected. Interestingly, in Chick Chorioallantoic Membrane (CAM) Assays, we found that TBX3 overexpressing cell lines gave rise to larger tumours in vivo. while the proliferation index was unaltered. Notably, increased invasion and migration suggest that such cells have undergone an Epithelial-Mesenchymal transition (EMT) and in line with this, we find that overexpression of TBX3 leads to reduced expression of the epithelial cell marker, e-cadherin. Collectively, our data suggest TBX3 a possible role during pancreatic cancer EMT and deeper understanding of this process might help to identify new targets in the future.