PXD032993

PXD032993 is an original dataset announced via ProteomeXchange.

Title	The deubiquitinase USP13 maintains cancer cell stemness by promoting FASN stability in small cell lung cancer
Description	USP13 is significantly amplified in over 20% of lung cancer patients and critical for tumor progression. However, the functional role of USP13 in small cell lung cancer (SCLC) remains largely unclear. In this study, we found that the deubiquitinase USP13 is highly expressed in SCLC tumor samples and positively associated with poor prognosis in multiple cohorts. In vitro and in vivo depletion of USP13 inhibited SCLC cancer stem cells (CSCs) properties and tumorigenesis, and this inhibitory effect was rescued by reconstituted expression of wide type (WT) USP13 but not the enzyme-inactive USP13 mutant. Mechanistically, USP13 interacts with fatty acid synthase (FASN) and enhances FASN protein stability. FASN downregulation suppresses USP13-enhanced cell renewal regulator expression, sphere formation ability, and de novo fatty acids biogenesis. Accordingly, we found FASN expression is upregulated in surgical resected SCLC specimens, positively correlated with USP13, and associated with poor prognosis of SCLC patients. More importantly, the small molecule inhibitor of FASN, TVB-2640, significantly inhibits lipogenic phenotype and attenuates self-renewal ability and chemotherapy resistance in SCLC. Thus, our study highlights a critical role of the USP13-FASN-lipogenesis axis in SCLC cancer stemness maintenance and tumor growth, and reveals a potential combination therapy for SCLC patients.
HostingRepository	iProX
AnnounceDate	2022-04-06
AnnouncementXML	Submission_2022-11-02_21:56:21.299.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juhong Wang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-05 20:59:47	ID requested
⏵ 1	2022-11-02 21:56:22	announced

Wang J, Lin W, Li R, Cheng H, Sun S, Shao F, Yang Y, Zhang L, Feng X, Gao S, Gao Y, He J, The Deubiquitinase USP13 Maintains Cancer Cell Stemness by Promoting FASN Stability in Small Cell Lung Cancer. Front Oncol, 12():899987(2022) [pubmed]

submitter keyword: USP13, cancer stem cells, FASN, ubiquitylation, lipogenesis, TVB-2640, SCLC

Yibo Gao
contact affiliation	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
contact email	gaoyibo@cicams.ac.cn
lab head
Juhong Wang
contact affiliation	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
contact email	wjh402826@163.com
dataset submitter

iProX dataset URI