PXD002735

PXD002735 is an original dataset announced via ProteomeXchange.

Title	Quantitative Phosphoproteomics Reveals Genistein as a Modulator of Cell Cycle and DNA Damage Response Pathways
Description	Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anti-cancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anti-cancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in a TNBC cell line, MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. In the meantime, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, for the first time, our study present the evidence that genistein could inhibit TNBC cell growth by regulating the cell cycle and DNA damage response. Our findings help elucidate the mechanisms through which genistein exerts its anti-cancer effects in TNBC cells.
HostingRepository	PRIDE
AnnounceDate	2016-01-26
AnnouncementXML	Submission_2016-01-26_03:04:21.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yi Fang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; phosphorylated residue; TMT6plex-126 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-17 01:44:08	ID requested
⏵ 1	2016-01-26 03:04:22	announced

Fang Y, Zhang Q, Wang X, Yang X, Wang X, Huang Z, Jiao Y, Wang J, Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells. Int J Oncol, 48(3):1016-28(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Genistein, MDA-MB-231, Triple Negative Breast Cancer, ATR, CKD1, LC-MS/MS, Phosphorylation

Jing Wang
contact affiliation	Department of breast surgical oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
contact email	wangjing.cicams@gmail.com
lab head
Yi Fang
contact affiliation	Chinese Academy of Medical Sciences and Peking Union Medical College
contact email	fangyi.cicams@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002735
     1. Label: PRIDE project
     2. Name: Quantitative Phosphoproteomics Reveals Genistein as a Modulator of Cell Cycle and DNA Damage Response Pathways