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Published on: July 21, 2018
Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis
Li Ma1, Yongzhen Tao, Angeles Duran
1Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|February 5, 2013
Summary
Protein kinase C zeta (PKCζ) deficiency allows cancer cells to adapt metabolism, utilizing glutamine via the serine biosynthetic pathway. Loss of PKCζ enhances tumor growth, indicating its role as a metabolic tumor suppressor.
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Tumor cells exhibit high metabolic demands and adapt to nutrient stress for survival and proliferation.
- Metabolic reprogramming is a hallmark of cancer, enabling sustained growth under challenging conditions.
Purpose of the Study:
- To investigate the role of Protein Kinase C zeta (PKCζ) in regulating cancer cell metabolism and its impact on tumorigenesis.
- To elucidate the molecular mechanisms by which PKCζ influences metabolic pathways crucial for cancer cell survival.
Main Methods:
- Studied the effect of PKCζ deficiency on cancer cell metabolism, focusing on glutamine utilization and the serine biosynthetic pathway.
- Analyzed the expression and activity of key enzymes PHGDH and PSAT1 in response to PKCζ levels.
- Utilized mouse models of intestinal tumorigenesis and analyzed human intestinal tumor samples.
Main Results:
- PKCζ deficiency promotes metabolic plasticity, enabling cancer cells to use glutamine via the serine biosynthetic pathway when glucose is limited.
- PKCζ represses PHGDH and PSAT1 expression and inhibits PHGDH activity through phosphorylation.
- Loss of PKCζ in mice leads to increased intestinal tumorigenesis and elevated PHGDH and PSAT1 levels.
- Low PKCζ levels in human cancer patients correlate with poor prognosis and are associated with PHGDH levels.
Conclusions:
- PKCζ acts as a critical metabolic tumor suppressor in both mouse and human cancers.
- PKCζ regulates cancer cell metabolism by controlling the serine biosynthetic pathway, impacting tumor growth and patient outcomes.
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