FIG 8.

Working model of the involvement of adhesion molecule-mediated Hippo pathway modulation in the regulation of cell proliferation and survival in WT-BEC and EOMA cells as well as the role of YM155 in the modulation of the Hippo pathway in EOMA cells. (A) WT-BEC exhibit a contact-inhibited phenotype, with the cells expressing optimal levels of CD31 and VE-cadherin, low levels of survivin, nondetectable levels of Ajuba (dashed lines), moderate levels of active caspases, and reduced nuclear YAP and increased cytoplasmic P-YAP levels, consistent with an active Hippo pathway. (B) Compared to WT-BEC, EOMA cells exhibit decreased contact inhibition and junctional molecule expression, resulting in downregulation of the Hippo pathway with increases in survivin, Ajuba (thick lines), and MMP expression levels and increased YAP nuclear translocation, suppressing caspase-mediated apoptosis and increasing proliferation. (C) EOMA cells treated with YM155 or transfected with survivin siRNA exhibit increased contact inhibition and junctional molecule expression resulting from increased CD31 and VE-cadherin expression levels and decreased survivin, Ajuba (dashed lines), and nuclear YAP expression levels, resulting in upregulation of the Hippo pathway, which in turn results in increased cytoplasmic P-YAP and decreased MMP2 expression levels and caspase-mediated apoptosis. (WT-BEC are not affected by YM155 treatment.)