PI3K/AKT/PTEN Signaling as a Molecular Target in Leukemia Angiogenesis

Abstract

PI3K/AKT/PTEN pathway is important in the regulation of angiogenesis mediated by vascular endothelial growth factor in many tumors including leukemia. The signaling pathway is activated in leukemia patients as well as leukemia cell lines together with a decrease in the expression of PTEN gene. The mechanism by which the signaling pathway regulates angiogenesis remains to be further elucidated. However, it has become an attractive target for drug therapy against leukemia, because angiogenesis is a key process in malignant cell growth. In this paper, we will focus on the roles and mechanisms of PI3K/AKT/PTEN pathway in regulating angiogenesis.

Figure 1

Schematic representation of PI3K/AKT/PTEN signaling. Examples of molecules known to act on angiogenesis via PI3K/AKT regulatory pathways are shown.

Figure 2

Representation of subclass molecules of PI3K. PI3K is composed of three subclasses based on the substrate, structure, distribution, and mechanism of activation.

Figure 3

Schematic structures of AKT1 (a) and PTEN (b) protein. The predicted consensual domain structures for each protein are depicted. PH domain: pleckstrin homology domain; C2 domain: a protein structural domain involved in targeting proteins to cell membranes; PDZ: a common structural domain in signaling proteins (PSD95, Dlg, ZO-1, etc.).