Figure 8.

Schematic representation of Ena/VASP proteins in FA of pericytes and tumor growth. VASP binds vinculin by virtue of its EVH1 and EVH2 domains. FA assembly also requires VASP-Rac1 interaction and Rac1 activation as revealed by defective FA phenotypes induced by siRNA targeting of VASP or Rac1 and rescue of the VASP siRNA defective FA phenotype by constitutively active Rac1. Perturbation of this signaling paradigm in vivo using the dominant negative EVH2 domain of VASP impairs FA and cell spreading of tumor associated myofibroblasts, thereby culminating in altered pericyte recruitment to tumor vasculature, reduced tumor angiogenesis, and impaired tumor growth. Myofibroblasts also likely influence tumor growth through angiogenesis-independent mechanisms as well (not shown).