A New Twist in Protein Kinase B/Akt Signaling: Role of Altered Cancer Cell Metabolism in Akt-Mediated Therapy Resistance.
Akt
DDR
DNA repair
antioxidant defense
chromatin modifications
energy metabolism
metabolism
metabolites
protein modifications
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
13 Nov 2020
13 Nov 2020
Historique:
received:
16
09
2020
revised:
23
10
2020
accepted:
09
11
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
4
3
2021
Statut:
epublish
Résumé
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 and cancer cell metabolism, focusing on antioxidant defense and DSB repair. Furthermore, the review highlights potential connections between deregulated Akt, cancer cell metabolism and therapy resistance of cancer cells through altered DSB repair and discusses potential resulting therapeutic implications.
Identifiants
pubmed: 33202866
pii: ijms21228563
doi: 10.3390/ijms21228563
pmc: PMC7697684
pii:
doi:
Substances chimiques
Antioxidants
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : GRK1739/2
Organisme : Horizon 2020
ID : 860245
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