The characterization of the molecular mechanisms by which dysregulation of pancreatic cells lead to cancer development and metastasis is of a major importance. In our previous research, we determined that PTP-PEST, a cytosolic tyrosine phosphatase, can regulate cellular motility via the regulation of cellular focal adhesion complex turnover (Angers-Loustau A, 1999). In addition, PTP-PEST has an essential dual role in the forward protrusion and also rear detachment of focal points via the regulation of VAV2 and p190RhoGAP (Sastry SK, 2006).
Interestingly, we found that PTP-PEST modulates the WASP protein that associates with Arp2/3, which is required at the actin nucleation site (Cote et al., 2002). The effect is therefore an alteration of cellular adhesion and motility, a feature typically found in metastatic cancer cells. Furthermore, Taieb et al. determined that PTP-PEST is associated with ArgBP2 signalling which regulates pancreatic cell mobility which when dysregulated could lead to metastasis (Taieb D, 2008).
Based on these facts, we are currently investigating a potential link between PTP-PEST and the progression of pancreatic cancer using the CRISPR/Cas system in addition to novel mouse models. In addition to in vitro and in vivo studies, an on-going collaboration with Dr. George Zogopoulos will shed light on novel molecular markers of pancreatic cancer using patient-derived xenografts.