PXD036977

PXD036977 is an original dataset announced via ProteomeXchange.

Title	Proteomic of huh7 grown in normal and glucose-deficient conditions
Description	Tumor cell metabolic plasticity is essential for tumor progression and therapeutic response, but the mechanism for regulation of metabolic plasticity remain poorly explored. Here, we identify PROX1 as an essential determinant for tumor metabolic plasticity. Notably, PROX1 is significantly reduced in response to metabolic stress or AMPK activation and is elevated in LKB1-deficient tumors in mice and human. Furthermore, the Ser79 phosphorylation of PROX1 by AMPK significantly alters its protein activity and allows a rapid recruitment of CUL4-DDB1 E3 ubiquitin ligase to promote PROX1 degradation under glucose starvation, a critical event that drives BCAA metabolism rewiring to suppress mTOR signaling. Importantly, PROX1 loss or Ser79 phosphorylation in HCC shows therapeutic resistance to metformin. Consistently, genetic ablation of PROX1 renders LKB1‐deficient KRAS-driven lung cancer resistant to phenformin treatment. Conversely, mice harboring non-phosphorylated PROX1 mutant or LKB1 mutant exhibit high PROX1 stabilization, promoting liver and lung cancer progression. Clinically, AMPK-PROX1 axis in human cancers is important for patient clinical outcomes. Collectively, our results demonstrate that the deficiency in the LKB1-AMPK axis in cancers reactivates PROX1 to sustain intracellular BCAA pools, resulting in enhanced mTOR signaling, and facilitating tumorigenesis and aggressiveness.
HostingRepository	PRIDE
AnnounceDate	2022-09-27
AnnouncementXML	Submission_2022-09-27_05:09:07.621.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fan Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-25 14:33:26	ID requested
⏵ 1	2022-09-27 05:09:07	announced

Dataset with its publication pending

submitter keyword: human, liver, huh7

Yang Feng Liu
contact affiliation	Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
contact email	lyf7858188@163.com
lab head
Fan Wang
contact affiliation	Renji-MedX Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
contact email	1606826420@qq.com
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/2022/09/PXD036977

PRIDE project URI

• PRIDE
  1. PXD036977
     1. Label: PRIDE project
     2. Name: Proteomic of huh7 grown in normal and glucose-deficient conditions