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Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-20 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Harmful effects of high fructose intake on health have been widely reported. Although fructose is known to promote cancer, little is known about the underlying mechanisms. Here, we found that fructose triggers breast cancer metastasis through the ketohexokinase-A signaling pathway. Molecular experiments showed that ketohexokinase-A, rather than ketohexokinase-C, is necessary and sufficient for fructose-induced cell invasion. Ketohexokinase-A-overexpressing breast cancer was found to be highly metastatic in fructose-fed mice. Mechanistically, cytoplasmic ketohexokinase-A enters into the nucleus during fructose stimulation, which is mediated by LRRC59 and KPNB1. In the nucleus, ketohexokinase-A phosphorylates YWHAH at Ser25 and the YWHAH recruits SLUG to the CDH1 promoter, which triggers cell migration. This study provides the effect of nutrition on breast cancer metastasis. High intake of fructose should be restricted in cancer patients to reduce the risk of metastasis. From a therapeutic perspective, the ketohexokinase-A signaling pathway could be a potential target to prevent cancer metastasis.<br />Apart from the enzymatic role of ketohexokinase isoform A (KHK-A) in fructose metabolism the alternative physiological functions of the enzyme are unclear. Here, the authors show that KHK-A mediates fructose-induced metastasis in breast cancer through a nuclear role in repressing the transcriptional activity of the cell-adhesion molecule CDH1.
- Subjects :
- 0301 basic medicine
General Physics and Astronomy
Metastasis
CDH1
Mice
chemistry.chemical_compound
0302 clinical medicine
Medicine
Neoplasm Metastasis
Phosphorylation
Nuclear protein
lcsh:Science
Multidisciplinary
biology
Cell migration
beta Karyopherins
Isoenzymes
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Female
Signal transduction
Signal Transduction
Science
Breast Neoplasms
Fructose
Article
General Biochemistry, Genetics and Molecular Biology
Fructokinases
03 medical and health sciences
Breast cancer
Cell Line, Tumor
Animals
Humans
Neoplasm Invasiveness
Cell Nucleus
business.industry
Mammary Neoplasms, Experimental
Membrane Proteins
Cancer
General Chemistry
medicine.disease
030104 developmental biology
14-3-3 Proteins
chemistry
Carcinogens
biology.protein
Cancer research
lcsh:Q
business
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....1f8041f84cd86256ac43e8ad267d1315