Abstract 1276: TRAIL-induced p38 activation responsible for increases of Akt catalytic and Invasive activity

Abstract

Abstract In this paper, we demonstrate that TRAIL-induced p38 activation is responsible for the increases of Akt catalytic activity and invasive activity. For the confirmation of increases of Akt catalytic and invasive activity induced by TRAIL-induced p38 activation, immune complex kinase assay and invasion assay was used. Previously, we observed that TRAIL induces acquired TRAIL resistance with increased Akt phosphorylation resulting from Src-PI3K-Akt signaling pathways mediating by c-Cbl. c-Cbl, an ubiquitously expressed cytoplasmic adaptor protein was shown to be involved in the rapid degradation of TRAIL receptors and simultaneously in the Akt phosphorylation during TRAIL treatment. However, Akt phosphorylation did not have an exclusive role for acquired TRAIL resistance. Like Akt catalytic activation during metabolic oxidative stress, TRAIL induced dramatically Akt catalytic activation in TRAIL-sensitive cells, whereas TRAIL did not induce Akt catalytic activation in TRAIL-resistant cells, suggesting Akt catalytic activation during TRAIL-induced apoptosis is likely to have a role of compensation for cell homeostasis. Our studies also reveal that p38 activation during TRAIL treatment is responsible for the increases of Akt catalytic and invasive activity. Bo K. Sun and Joo-Hang Kim are equally contributed to this work. Correspondence: Jae J Song (jjs109@yuhs.ac) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1276.