A New Twist in Protein Kinase B/Akt Signaling: Role of Altered Cancer Cell Metabolism in Akt-Mediated Therapy Resistance.

International Journal of Molecular Sciences
Isabell GöttingJohann Matschke

Abstract

Cancer resistance to chemotherapy, radiotherapy and molecular-targeted agents is a major obstacle to successful cancer therapy. Herein, aberrant activation of the phosphatidyl-inositol-3-kinase (PI3K)/protein kinase B (Akt) pathway is one of the most frequently deregulated pathways in cancer cells and has been associated with multiple aspects of therapy resistance. These include, for example, survival under stress conditions, apoptosis resistance, activation of the cellular response to DNA damage and repair of radiation-induced or chemotherapy-induced DNA damage, particularly DNA double strand breaks (DSB). One further important, yet not much investigated aspect of Akt-dependent signaling is the regulation of cell metabolism. In fact, many Akt target proteins are part of or involved in the regulation of metabolic pathways. Furthermore, recent studies revealed the importance of certain metabolites for protection against therapy-induced cell stress and the repair of therapy-induced DNA damage. Thus far, the likely interaction between deregulated activation of Akt, altered cancer metabolism and therapy resistance is not yet well understood. The present review describes the documented interactions between Akt, its target proteins a...Continue Reading

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Citations

Dec 5, 2020·International Journal of Molecular Sciences·Yanzhen SunHao Hu
Jun 11, 2021·Biochemical Society Transactions·Johann MatschkeVerena Jendrossek
Jul 10, 2021·Signal Transduction and Targeted Therapy·Ruixue Huang, Ping-Kun Zhou
Aug 8, 2021·International Journal of Molecular Sciences·Titanilla DankóAnna Sebestyén

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Methods Mentioned

BETA
ubiquitination
nuclear translocation
acetylation
histone acetylation

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