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Article: TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression

TitleTROAP switches DYRK1 activity to drive hepatocellular carcinoma progression
Authors
Issue Date2021
PublisherNature 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?
AbstractHepatocellular 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 Identifierhttp://hdl.handle.net/10722/300844
ISSN
2020 Impact Factor: 8.469
2020 SCImago Journal Rankings: 2.482
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, L-
dc.contributor.authorWei, JR-
dc.contributor.authorSong, Y-
dc.contributor.authorFang, S-
dc.contributor.authorDu, Y-
dc.contributor.authorLi, Z-
dc.contributor.authorZeng, TT-
dc.contributor.authorZhu, YH-
dc.contributor.authorLi, Y-
dc.contributor.authorGuan, XY-
dc.date.accessioned2021-07-06T03:11:00Z-
dc.date.available2021-07-06T03:11:00Z-
dc.date.issued2021-
dc.identifier.citationCell Death & Disease, 2021, v. 12, p. article no. 125-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/300844-
dc.description.abstractHepatocellular 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.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleTROAP switches DYRK1 activity to drive hepatocellular carcinoma progression-
dc.typeArticle-
dc.identifier.emailLi, L: lilei728@HKUCC-COM.hku.hk-
dc.identifier.emailGuan, XY: xyguan@hku.hk-
dc.identifier.authorityGuan, XY=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-021-03422-3-
dc.identifier.pmid33500384-
dc.identifier.pmcidPMC7838256-
dc.identifier.scopuseid_2-s2.0-85099819588-
dc.identifier.hkuros323258-
dc.identifier.volume12-
dc.identifier.spagearticle no. 125-
dc.identifier.epagearticle no. 125-
dc.publisher.placeUnited Kingdom-

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