Abstract 4522: Akt2 and acid ceramidase cooperate to induce malignant transformation

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The ability of Akt 2 and acid ceramidase (ASAH1) to cooperate and induce malignant transformation is not known. Here we show that in immortalized, non-transformed cells, ectopic co-expression of Akt2 and ASAH1 is significantly more effective than expression of each gene alone at inducing cell invasion and at conferring resistance to apoptosis. Consistent with these observations, siRNA-mediated depletion of both Akt2 and ASAH1 is much more potent than depleting each alone at inhibiting cell viability/proliferation and cell invasion. Furthermore, pharmacological inhibitors of Akt (TCN or MK-2206) and ASAH1 (B13) synergize to inhibit cell viability/proliferation, and combinations of these drugs are more effective than single agent treatments at inhibiting cell invasion. Taken together, the results suggest that these two enzymes cooperate to induce malignant transformation and warrant further preclinical studies to evaluate the potential of combining inhibitors of Akt and ASAH1 to treat cancer. Citation Format: Said M. Sebti, Norbert Berndt, Ronil Patel, Hua Yang, Maria Balasis. Akt2 and acid ceramidase cooperate to induce malignant transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4522. doi:10.1158/1538-7445.AM2014-4522