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Role of protein-tyrosine phosphatases in angiogenesis

Final Report Summary - PTPS IN ANGIOGENESIS (Role of protein-tyrosine phosphatases in angiogenesis)

It is estimated that more than 500 million people will benefit from anti- or pro-angiogenesis treatments in the coming decades. Angiogenesis is the formation of new blood vessels from pre-existing ones and is involved in different physiological and pathological processes. Tyrosine phosphorylation is a reversible process, mediated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) that regulate critical cell signalling pathways. Both PTKs and PTPs play a vital regulatory role in many important biological processes including proliferation, migration, differentiation, and apoptosis and their deregulation can lead to diseases such as cancer.

Although the role of several PTKs in angiogenesis is well studied, little is known about the role of specific PTPs in this process. Our goals were to determine the biological roles of specific PTPs in endothelial cells in vitro and in vivo. We assessed the expression of specific PTPs in endothelial cells, developed shRNA systems to knockdown PTPs and tested the effect of knockdown of PTP?, PTPN14 and PTP1B in a 3D in vitro spheroid assay as well as using in vivo assays. We found no significant effect of knockdown of these PTPs in these assays suggesting a level of redundancy among PTPs in angiogenesis and a need for knocking more than one PTP in ECs.