Akt2 and acid ceramidase cooperate to induce cell invasion and resistance to apoptosis
| Autor: | Norbert Berndt, Said M. Sebti, Maria E. Balasis, Ronil Patel, Hua Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Acid Ceramidase
Cell Survival AKT2 Apoptosis Biology Protein Serine-Threonine Kinases Malignant transformation Propanolamines Report Cell Line Tumor Humans Neoplasm Invasiveness Viability assay RNA Small Interfering Molecular Biology Protein kinase B Cell Proliferation Antibiotics Antineoplastic Cell growth Drug Synergism Cell Biology Molecular biology Amides Peptide Fragments Doxorubicin Drug Resistance Neoplasm Gene Knockdown Techniques Cancer cell Cancer research Heterocyclic Compounds 3-Ring Developmental Biology |
| Popis: | Both Akt 2 and acid ceramidase (ASAH1) are found aberrantly overexpressed in cancer cells, but whether these two enzymes cooperate to induce malignant transformation is not known. We found 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. |
| Databáze: | OpenAIRE |
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