AKT: A Central Node in Complex Signaling Cascades

Akt (v-akt murine thymoma virus oncogene homologue) is a well-known serine-threonine kinase that functions as a central node in various important signal cascades involved in cellular maintenance. Akt has also been implicated in oncogenic malignancies as evidenced by protein overexpression, activation and somatic aberration of components in the phosphoinositide-3 kinase-Akt pathway. As such, Akt is a potential target in cancer therapy. Akt is frequently activated in human cancer tissues not only due to aberrant upstream signaling, but also by genetic mutations in AKT itself. This leads to the aberrant activation of pathways downstream of Akt that regulate cell-cycle progression and metabolism as well as activation of transcription factors that promote oncogenesis. In this review, we summarize previous research on Akt, including the molecular mechanisms underlying Akt signal transduction, as well as its physiologic roles and the pathologic consequences when dysregulated. We also discuss the roles of dysregulated protein overexpression/activation, increases in gene copy number, single nucleotide polymorphisms and the network of non-coding RNAs that regulate this pathway, with a particular focus on lung carcinomas. Finally, we discuss strategies that might lead to more effective targeting of Akt for clinical cancer therapy.