Analysis of a panel of tumor-derived cell lines demonstrated that 17KPC cells are specifically defective in their ability to form invadopodia rosettes and invade through Matrigel in a transwell assay, providing a potential link to our in vivo observations. Using antagomirs against miR-19, we demonstrated that miR-19 family miRNAs are key drivers of invadopodia formation and the invasive capacity of human and murine pancreatic cancer cells. Thus, we have identified a novel role for miR-19 in pancreatic cancer cells. In fact, few studies exist that link miR-19 to cancer cell invasion in any tumor type [36, 37]. Future studies will be required to validate the significance of miR-19 family miRNAs in the invasive phenotype of PDAC in vivo. In addition, expression profiling and proteomic studies will be required to identify the mechanisms through which miR-19 miRNAs regulate invadopodia formation and function. TIMP2, CST3, and TGM2 are all predicted targets of miR-19 that are also suppressors of invasion [37, 39, 62, 63] and could potentially explain the reduced invasiveness of 17KPC cell lines. Indeed, TGM2 is linked to miR-19-mediated invasion in colorectal cancer cells . However, immunoblotting and qRT-PCR experiments failed to detect any difference in expression between KPC and 17KPC cell lines (data not shown). Matrix metalloproteinases are also key drivers of invasion , and a survey of MMP-2, -7, -9, and MT1-MMP by qRT-PCR demonstrated no difference between KPC and 17KPC cell lines (data not shown). Given that our data point to a major effect of miR-19 on invadopodia formation and/or stability, and since none of the above factors are known to influence invadopodia, these negative findings are perhaps not surprising. Instead, they highlight the importance of the unbiased approaches stated above for elucidating the mechanisms responsible for the observed phenotypes.