Panagiotis Z. Anastasiadis, Ph.D.

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SUMMARY

The laboratory of Panagiotis (Panos) Z. Anastasiadis, Ph.D., is interested in elucidating the role of cadherin adhesion receptors, polarity proteins and Rho GTPases in human cancer. In particular, the lab is investigating adhesion-mediated signaling events that regulate cell growth, suppress cell motility and invasiveness, and promote the reorganization of the actin cytoskeleton.

Focus areas

• p120 catenin. A central player in adhesion-mediated signaling events is p120 catenin, a cadherin-binding partner that promotes cell adhesion by inhibiting cadherin endocytosis and by recruiting microtubules to the junctions. While these properties suggest a tumor suppressor function for p120, recent studies from Dr. Anastasiadis' lab indicate that p120 can also promote cancer progression, in part through the regulation of Rho GTPases and the subsequent reorganization of the actin cytoskeleton.

  Dr. Anastasiadis' research team is now trying to resolve the apparent paradox of p120's function in cancer, and has identified two spatially and functionally distinct p120 complexes. One is anti-tumorigenic, defined by the p120 partner PLEKHA7. The other is pro-tumorigenic, defined by increased p120 tyrosine phosphorylation by the oncogenic kinase Src. This work uncovers a new mechanism by which adhesion complexes affect cell behavior and reveals a surprising connection between adhesion complexes and miRNA biogenesis.

  Finally, the lab is also investigating the significance of both p120 and PLEKHA7 as biomarkers and molecular therapy targets in human cancer. Ongoing studies show that p120 tyrosine phosphorylation correlates with aggressiveness of brain cancers, and that restoration of PLEKHA7 function inhibits cancer cell growth.

• The cadherin-catenin complex. In addition to epithelial tumors, research is focused on the role of the cadherin-catenin complex in the progression of brain tumors. Cadherins and catenins are thought to play an important role in synaptogenesis and neuronal plasticity. However, deregulation of the cadherin-catenin complex may also promote brain tumor progression and the acquisition of an invasive phenotype.
• Rho GEFs and polarity complexes. More recently, the lab has systematically explored the function of Rho GEFs and polarity complexes in endothelial monolayer function and leakiness, directed cell migration, and glioma cell invasion and aggressiveness. The results clarified VEGF-mediated signaling leading to increased vascular leakiness, identified a novel member of the Crumbs polarity complex, and uncovered a novel target for glioma therapy.

Significance to patient care

Dr. Anastasiadis' research goal is to translate a better understanding of cell motility and invasiveness into targeted therapeutic treatments that block invasiveness and metastasis in cancer patients.