PXD042963

PXD042963 is an original dataset announced via ProteomeXchange.

Title	GP73-dependent regulation of exosome biogenesis promotes colorectal cancer liver metastasis
Description	Colorectal cancer (CRC) liver metastasis is the main cause of cancer-related mortality. The mechanisms by which cancer cells regulate liver microenvironment to promote cancer liver metastasis have been extensively studied. However, how the liver influences intercellular communication to support tumor liver metastasis remains largely unknown. Here, we link GP73, whose chronic upregulation in hepatocytes triggers non-obese NAFLD in mice, with exosome biogenesis and hence cancer liver metastasis. Plasma GP73 level and liver GP73 protein expression were significantly elevated in CRC patients with liver metastasis (CRLM) as compared with CRC patients without liver metastasis. Strikingly, mice with high liver GP73 expression induced by Ad5-GP73 injection exhibited significantly increased CRC liver metastasis in an exosome dependent manner. Notably, GP73 overlapped with endosomal compartments and promoted exosome production. Mechanistically, GP73 bound to cholesterol and modulated the cholesterol content in endosomal compartments/multivesicular bodies (MVBs). Quantitative proteomics profiling revealed that GP73 reshaped hepatocyte exosomal proteome and produces NAV2-containing exosomes. Clinically, serum GP73 levels correlated positively with serum exosome NAV2 levels in CRLM. In particular, exosomes from GP73-high livers promoted tumor cell invasiveness mainly through transferable NAV2. Knockdown liver NAV2 suppressed enhanced CRC liver metastasis in GP73-induced non-obese mice, and GP73 blockade significantly mitigated CRC liver metastasis enhancement in obese mice resulting from high-fat diet (HFD) or high-fructose diet (HFrD) feeding. Collectively, our findings provide novel insight into the roles of GP73 in exosome biogenesis and GP73 blockade may merit exploration as a potential therapeutic strategy for mitigating CRC liver metastasis.
HostingRepository	iProX
AnnounceDate	2023-06-13
AnnouncementXML	Submission_2023-10-17_19:36:45.019.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Linfei Huang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-13 19:15:54	ID requested
⏵ 1	2023-10-17 19:36:45	announced

Dataset with its publication pending

submitter keyword: GP73,Exosome,colerectal cancer,metastasis

Hui Zhong
contact affiliation	Beijing Institute of Biotechnology, Beijing, China
contact email	towall@yahoo.com
lab head
Linfei Huang
contact affiliation	Beijing Institute of Biotechnology, Beijing, China
contact email	huanglinfei_@163.com
dataset submitter

iProX dataset URI