Related Experiment Video
Updated: Feb 19, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth
D Ma1,2, X Chen1,2, P-Y Zhang1,2
1Digestive Cancer Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
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.
Insights
Dietary restriction (DR) suppresses tumor growth by activating the aldolase A (ALDOA)/DNA-dependent protein kinase (DNA-PK)/p53 pathway. This novel mechanism highlights how DR enhances the tumor suppressor p53
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Dietary restriction (DR) is known to delay tumor incidence and growth, but the underlying molecular mechanisms remain unclear.
- Understanding how DR exerts its antitumor effects is crucial for developing novel cancer therapies.
Purpose of the Study:
- To identify the novel signaling pathway responsible for the antitumor effects of dietary restriction.
- To elucidate the role of aldolase A (ALDOA) in mediating DR-induced tumor suppression.
Main Methods:
- Xenograft tumor models were used to study the effects of DR on tumor growth.
- Immunoprecipitation and Western blotting were employed to investigate protein interactions and activation.
- Analysis of aldolase A (ALDOA), DNA-dependent protein kinase (DNA-PK), and p53 expression and activity was performed.
Main Results:
- Dietary restriction upregulated aldolase A (ALDOA) expression in xenograft tumors.
- ALDOA was found to interact with and activate DNA-dependent protein kinase (DNA-PK).
- Activated DNA-PK phosphorylated and enhanced the activity of the tumor suppressor p53, leading to suppressed tumor growth. DR's antitumor effects were dependent on p53 presence.
Conclusions:
- The ALDOA/DNA-PK/p53 signaling pathway is a key mechanism through which dietary restriction exerts its antitumor effects.
- Aldolase A (ALDOA) acts as a crucial mediator, linking dietary restriction to the activation of the p53 tumor suppressor pathway.
- Targeting the ALDOA/DNA-PK/p53 axis may represent a promising therapeutic strategy for enhancing the benefits of dietary restriction in cancer treatment.
Related Concept Videos
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Negative Regulator Molecules
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
PI3K/mTOR/AKT Signaling Pathway
DNA Damage can Stall the Cell Cycle

