PXD035911
PXD035911 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | HK1 from HSC-derived extracellular vesicles promotes HCC progression |
| Description | Extracellular vesicles play crucial roles in intercellular communication in tumor microenvironment. Here, we demonstrate that in hepatic fibrosis, TGF-β stimulates the palmitoylation of hexokinase 1 (HK1) in hepatic stellate cells (HSCs), which facilitates the secretion of HK1 via large extracellular vesicles (lEVs) in a TSG101-dependent manner. The lEV HK1 is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, the nuclear receptor Nur77 transcriptionally activates the expression of depalmitoylase ABHD17B to inhibit HK1 palmitoylation, consequently attenuating HK1 release. However, TGF-β-activated Akt functionally represses Nur77 by inducing Nur77 phosphorylation and degradation. We identify a small molecule PDNPA that binds Nur77 to generate steric hindrance to block Akt targeting, thereby disrupting Akt-mediated Nur77 degradation and preserving Nur77 inhibition of HK1 release. Together, this study demonstrates an overlooked function of HK1 in HCC upon its release from HSCs and highlights PDNPA as a candidate compound for inhibiting HCC progression. |
| HostingRepository | iProX |
| AnnounceDate | 2022-08-09 |
| AnnouncementXML | Submission_2022-12-24_20:59:48.154.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Qitao Chen |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | TripleTOF 5600+; timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2022-08-09 04:31:53 | ID requested | |
| 1 | 2022-09-18 04:27:59 | announced | |
| ⏵ 2 | 2022-12-24 20:59:49 | announced | 2022-12-25: Update publication information. |
Publication List
| Chen QT, Zhang ZY, Huang QL, Chen HZ, Hong WB, Lin T, Zhao WX, Wang XM, Ju CY, Wu LZ, Huang YY, Hou PP, Wang WJ, Zhou D, Deng X, Wu Q, HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. Nat Metab, 4(10):1306-1321(2022) [pubmed] |
Keyword List
| submitter keyword: Hexokinase 1 (HK1), hepatic stellate cell (HSC), hepatocellular carcinoma (HCC), large extracellular vesicle (lEV)/small extracellular vesicles (sEV), fibrosis, nuclear receptor Nur77 |
Contact List
| Qiao Wu | |
|---|---|
| contact affiliation | School of Life Sciences, Xiamen University |
| contact email | qiaow@xmu.edu.cn |
| lab head | |
| Qitao Chen | |
| contact affiliation | School of Life Sciences, Xiamen University |
| contact email | chenqitao0714@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
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