PXD019946

PXD019946 is an original dataset announced via ProteomeXchange.

Title	Autophagy Deficiency Promotes Triple-Negative Breast Cancer Resistance to T Cell-Mediated Cytotoxicity by Blocking Tenascin-C Degradation
Description	Most triple-negative breast cancer (TNBC) patients fail to respond to T cell-mediated immunotherapies. Unfortunately, the molecular determinants are still poorly understood. Breast cancer is the disease genetically linked to a deficiency in autophagy. Here, we show that autophagy promotes tumour immune response, and autophagy defects inhibit T cell-mediated killing in TNBC tumours. Mechanistically, we identify Tenascin-C as a strong candidate for autophagy deficiency-mediated immunosuppression, in which Tenascin-C is Lys63-ubiquitinated by Skp2, particularly at Lys924 and Lys1882, thus promoting its recognition by p62 and leading to its selective autophagic degradation. High Tenascin-C expression is associated with poor prognosis and inversely correlated with LC3B expression and CD8+ T cells in TNBC patients. More importantly, inhibition of Tenascin-C in autophagy-impaired TNBC cells sensitizes T cell-mediated tumour killing and improves antitumour effects of single anti-PD1/PD-L1 therapy. Our results provide a potential strategy against TNBC with the combination of Tenascin-C blockade and immune checkpoint inhibitors.
HostingRepository	PRIDE
AnnounceDate	2020-08-05
AnnouncementXML	Submission_2020-08-04_23:09:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rong Deng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-22 03:10:25	ID requested
⏵ 1	2020-08-04 23:09:57	announced

Li ZL, Zhang HL, Huang Y, Huang JH, Sun P, Zhou NN, Chen YH, Mai J, Wang Y, Yu Y, Zhou LH, Li X, Yang D, Peng XD, Feng GK, Tang J, Zhu XF, Deng R, Autophagy deficiency promotes triple-negative breast cancer resistance to T cell-mediated cytotoxicity by blocking tenascin-C degradation. Nat Commun, 11(1):3806(2020) [pubmed]

submitter keyword: autophagy deficiency, TNBC, Tenascin-C, T cell-mediated killing, immune checkpoint inhibitors

Rong Deng
contact affiliation	State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
contact email	dengrong@sysucc.org.cn
lab head
Rong Deng
contact affiliation	Sun Yat-sen University Cancer Center
contact email	dengrong@sysucc.org.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/08/PXD019946

PRIDE project URI

• PRIDE
  1. PXD019946
     1. Label: PRIDE project
     2. Name: Autophagy Deficiency Promotes Triple-Negative Breast Cancer Resistance to T Cell-Mediated Cytotoxicity by Blocking Tenascin-C Degradation