PXD043500

PXD043500 is an original dataset announced via ProteomeXchange.

Title	in vitro kinase assays Identified of STAT1 phosphorylation sites-mediated LATS2
Description	LATS1/2 are frequently down-regulated or mutated in endometrial cancer (EC), yet their exact role in endometrial tumor progression remains unclear. In this study, we unexpectedly discovered a new function of LATS1/2 in regulating MHC class I expression in EC. Knockout of LATS1/2 in EC cells led to significant down-regulation of multiple genes within the MHC/HLA Class I family, which weakened the killing effects of PBMCs on tumor cells. Importantly, we found that the regulation of MHC/HLA expression by LATS1/2 does not depend on the classical Hippo pathway but rather involves their direct interaction with STAT1. This interaction causes STAT1 to be phosphorylated at Ser727 or Ser532, promoting its accumulation and movement into the nucleus and enhancing the transcriptional activation of IRF1/NLRC5 on MHC-I. Additionally, we demonstrated that the kinase-dead mutant LATS1/2 weakens STAT1 phosphorylation at Ser727, supporting our findings. Our results show a positive correlation between the expression levels of LATS1/2, MHC-I, CD8, and p-STAT1 in tissue samples of EC, providing further evidence to support our discoveries. Overall, our findings reveal novel molecular mechanisms underlying tumor immunogenicity deficiency and suggest that LATS1/2 may serve as an immunotherapy biomarker for targeting EC.
HostingRepository	PRIDE
AnnounceDate	2024-06-16
AnnouncementXML	Submission_2024-06-16_01:06:17.483.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Huiru Sun
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-03 08:32:01	ID requested
⏵ 1	2024-06-16 01:06:18	announced

Yang Q, Lv Z, Wang M, Kong M, Zhong C, Gao K, Wan X, LATS1/2 loss promote tumor immune evasion in endometrial cancer through downregulating MHC-I expression. J Exp Clin Cancer Res, 43(1):54(2024) [pubmed]

10.1186/s13046-024-02979-z;

submitter keyword: in vitro phosphorylation,STAT1, LATS2

Qianlan Yang
contact affiliation	Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University，Shanghai，China
contact email	qlyang2013@126.com
lab head
Huiru Sun
contact affiliation	Fudan University
contact email	21112030011@m.fudan.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043500
     1. Label: PRIDE project
     2. Name: in vitro kinase assays Identified of STAT1 phosphorylation sites-mediated LATS2