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- Publisher Website: 10.1038/s41419-021-03422-3
- Scopus: eid_2-s2.0-85099819588
- PMID: 33500384
- WOS: WOS:000613890500001
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Article: TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression
Title | TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression |
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Authors | |
Issue Date | 2021 |
Publisher | Nature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html |
Citation | Cell Death & Disease, 2021, v. 12, p. article no. 125 How to Cite? |
Abstract | Hepatocellular carcinoma (HCC) is one of the common malignancy and lacks effective therapeutic targets. Here, we demonstrated that ectopic expression of trophinin-associated protein (TROAP) dramatically drove HCC cell growth assessed by foci formation in monolayer culture, colony formation in soft agar and orthotopic liver transplantation in nude mice. Inversely, silencing TROAP expression with short-hairpin RNA attenuated the malignant proliferation of HCC cells in vitro and in vivo. Next, mechanistic investigation revealed that TROAP directly bound to dual specificity tyrosine phosphorylation regulated kinase 1A/B (DYRK1A/B), resulting in the cytoplasmic retention of proteins DYRK1A/B and promoting cell cycle process via activation of Akt/GSK-3β signaling. Combination of cisplatin with an inhibitor of DYRK1 AZ191 effectively inhibited tumor growth in mouse model for HCC cells with high level of TROAP. Clinically, TROAP was significantly upregulated by miR-142-5p in HCC tissues, which predicted the poor survival of patients with HCC. Therefore, TROAP/DYRK1/Akt axis may be a promising therapeutic target and prognostic indicator for patients with HCC. |
Persistent Identifier | http://hdl.handle.net/10722/300844 |
ISSN | 2023 Impact Factor: 8.1 2023 SCImago Journal Rankings: 2.447 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Li, L | - |
dc.contributor.author | Wei, JR | - |
dc.contributor.author | Song, Y | - |
dc.contributor.author | Fang, S | - |
dc.contributor.author | Du, Y | - |
dc.contributor.author | Li, Z | - |
dc.contributor.author | Zeng, TT | - |
dc.contributor.author | Zhu, YH | - |
dc.contributor.author | Li, Y | - |
dc.contributor.author | Guan, XY | - |
dc.date.accessioned | 2021-07-06T03:11:00Z | - |
dc.date.available | 2021-07-06T03:11:00Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Cell Death & Disease, 2021, v. 12, p. article no. 125 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | http://hdl.handle.net/10722/300844 | - |
dc.description.abstract | Hepatocellular carcinoma (HCC) is one of the common malignancy and lacks effective therapeutic targets. Here, we demonstrated that ectopic expression of trophinin-associated protein (TROAP) dramatically drove HCC cell growth assessed by foci formation in monolayer culture, colony formation in soft agar and orthotopic liver transplantation in nude mice. Inversely, silencing TROAP expression with short-hairpin RNA attenuated the malignant proliferation of HCC cells in vitro and in vivo. Next, mechanistic investigation revealed that TROAP directly bound to dual specificity tyrosine phosphorylation regulated kinase 1A/B (DYRK1A/B), resulting in the cytoplasmic retention of proteins DYRK1A/B and promoting cell cycle process via activation of Akt/GSK-3β signaling. Combination of cisplatin with an inhibitor of DYRK1 AZ191 effectively inhibited tumor growth in mouse model for HCC cells with high level of TROAP. Clinically, TROAP was significantly upregulated by miR-142-5p in HCC tissues, which predicted the poor survival of patients with HCC. Therefore, TROAP/DYRK1/Akt axis may be a promising therapeutic target and prognostic indicator for patients with HCC. | - |
dc.language | eng | - |
dc.publisher | Nature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html | - |
dc.relation.ispartof | Cell Death & Disease | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression | - |
dc.type | Article | - |
dc.identifier.email | Li, L: lilei728@HKUCC-COM.hku.hk | - |
dc.identifier.email | Guan, XY: xyguan@hku.hk | - |
dc.identifier.authority | Guan, XY=rp00454 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41419-021-03422-3 | - |
dc.identifier.pmid | 33500384 | - |
dc.identifier.pmcid | PMC7838256 | - |
dc.identifier.scopus | eid_2-s2.0-85099819588 | - |
dc.identifier.hkuros | 323258 | - |
dc.identifier.volume | 12 | - |
dc.identifier.spage | article no. 125 | - |
dc.identifier.epage | article no. 125 | - |
dc.identifier.isi | WOS:000613890500001 | - |
dc.publisher.place | United Kingdom | - |