PXD021035

PXD021035 is an original dataset announced via ProteomeXchange.

Title	Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer
Description	Harmful effects of high fructose intake on health have been widely reported in epidemiological and laboratory studies. Although it has been reported that fructose promotes cancer development and progression, little is known about the underlying molecular 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. An orthotopic xenograft experiment revealed that ketohexokinase16 A-overexpressing breast cancer is highly metastatic in fructose-fed mice. Mechanistically, ketohexokinase-A moves from the cytoplasm to the nucleus during fructose stimulation, which is mediated by the nuclear importers LRRC59 and KPNB1. In the nucleus, ketohexokinase-A phosphorylates YWHAH at Ser25 and, in turn, YWHAH recruits SLUG to the CDH1 promoter, 20 which weakens cell adhesion and triggers cell migration. This study provides a new insight into 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.
HostingRepository	PRIDE
AnnounceDate	2020-11-09
AnnouncementXML	Submission_2020-11-09_07:46:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jongmin Woo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-20 23:03:02	ID requested
⏵ 1	2020-11-09 07:46:38	announced

Kim J, Kang J, Kang YL, Woo J, Kim Y, Huh J, Park JW, Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer. Nat Commun, 11(1):5436(2020) [pubmed]

submitter keyword: breast cancer metastasis

fructose

ketohexokinase-A

nuclear translocation

serine kinase

Jongmin Woo
contact affiliation	Pacific Northwest National Laboratory
contact email	jongmin.woo@pnnl.gov
lab head
Jongmin Woo
contact affiliation	Pacific Northwest National Laboratory
contact email	jongminw@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021035
     1. Label: PRIDE project
     2. Name: Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer