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Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth
- Source :
- Oncogene. 37:1041-1048
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinoma, Hepatocellular
Mice, Nude
Apoptosis
DNA-Activated Protein Kinase
Mice
03 medical and health sciences
Downregulation and upregulation
Cell Movement
Fructose-Bisphosphate Aldolase
Biomarkers, Tumor
Tumor Cells, Cultured
Genetics
Animals
Humans
Neoplasm Invasiveness
Protein kinase A
Molecular Biology
Caloric Restriction
Cell Proliferation
Mice, Inbred BALB C
biology
Oncogene
Cell growth
Liver Neoplasms
Aldolase A
Nuclear Proteins
Xenograft Model Antitumor Assays
Molecular biology
Diet
Gene Expression Regulation, Neoplastic
030104 developmental biology
biology.protein
Phosphorylation
Female
Tumor Suppressor Protein p53
Signal transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....d39d19868c228228ac1d8ccb828f6ca1