PXD062501

PXD062501 is an original dataset announced via ProteomeXchange.

Title	NANS suppresses NF-κB signaling to promote ferroptosis by perturbing iron homeostasis
Description	During metastasis, cancer cells face significant survival pressures, including treatment-induced ferroptosis. Adaptation to ferroptosis stress orchestrates the metastasis of colorectal cancer (CRC) cells. However, the reciprocal regulatory mechanisms of ferroptosis and metastasis remain unknown. Here, through a CRISPR–Cas9 screen, we discovered that N-acetylneuraminate synthase (NANS) is a positive regulator of ferroptosis in CRC, regardless of its metabolic function. Moreover, NANS expression is downregulated and is clinically associated with poor prognosis in CRC patients. In a ferroptotic stress environment, NANS is phosphorylated by cyclin-dependent kinase 1 (CDK1) at serine 275 (S275), and phosphorylated NANS (NANS pS275) dissociates from TAK1 and is subsequently ubiquitinated by the E3 ligase ubiquitin-conjugating enzyme E2 N (UBE2N) at lysine 246 (K246) for degradation, which further activates TAK1 and nuclear factor κB (NF-κB) signaling and the expression of the ferroptosis negative regulatory factor FTH1, resulting in ferroptosis resistance and finally promoting metastasis. Furthermore, the NANS pS275 intensity is correlated with the degree of malignancy and the prognosis of CRC patients. Our study revealed that NANS inhibits CRC metastasis by promoting ferroptosis and that the CDK1-mediated phosphorylation of NANS at S275 may guide the utilization of chemical compounds to promote ferroptosis and thus block CRC metastasis.
HostingRepository	PRIDE
AnnounceDate	2025-05-08
AnnouncementXML	Submission_2025-05-07_17:24:39.181.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ziyang Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-01 23:28:04	ID requested
⏵ 1	2025-05-07 17:24:39	announced

10.1016/J.CELREP.2025.115701;

submitter keyword: colorectal cancer metastasis., NF-κB signaling, CDK1, iron homeostasis,Ferroptosis, NANS

Ziyang Wang
contact affiliation	The First Affiliated Hospital, Sun Yat-sen University
contact email	wangzy256@mail.sysu.edu.cn
lab head
Ziyang Wang
contact affiliation	Sun Yat-sen University
contact email	wangzy256@mail.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062501
     1. Label: PRIDE project
     2. Name: NANS suppresses NF-κB signaling to promote ferroptosis by perturbing iron homeostasis