FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2798034858> ?p ?o ?g. }

• W2798034858 abstract "Protein tyrosine phosphatase of regenerating liver 3 (PRL-3) is overexpressed in a subset of AML patients with inferior prognosis, representing an attractive therapeutic target. However, due to relatively shallow pocket of the catalytic site of PRL-3, it is difficult to develop selective small molecule inhibitor. In this study, we performed whole-genome lentiviral shRNA library screening to discover synthetic lethal target to PRL-3 in AML. We used specific small molecule inhibitors to validate the synthetic lethality in human PRL-3 high vs PRL-3 low human AML cell lines and primary bone marrow cells from AML patients. AML mouse xenograft model was used to examine the in vivo synergism. The list of genes depleted in TF1-hPRL3 cells was particularly enriched for members involved in WNT/β-catenin pathway and AKT/mTOR signaling. These findings prompted us to explore the impact of AKT/mTOR signaling inhibition in PRL-3 high AML cells in combination with WNT/β-catenin inhibitor. VS-5584, a novel, highly selective dual PI3K/mTOR inhibitor, and ICG-001, a WNT inhibitor, were used as a combination therapy. A synthetic lethal interaction between mTOR/AKT pathway inhibition and WNT/β-catenin was validated by a variety of cellular assays. Notably, we found that treatment with these two drugs significantly reduced leukemic burden and prolonged survival of mice transplanted with human PRL-3 high AML cells, but not with PRL-3 low AML cells. In summary, our results support the existence of cooperative signaling networks between AKT/mTOR and WNT/β-catenin pathways in PRL-3 high AML cells. Simultaneous inhibition of these two pathways could achieve robust clinical efficacy for this subtype of AML patient with high PRL-3 expression and warrant further clinical investigation." @default.
• W2798034858 created "2018-04-24" @default.
• W2798034858 creator A5003427098 @default.
• W2798034858 creator A5004994169 @default.
• W2798034858 creator A5012262880 @default.
• W2798034858 creator A5035638353 @default.
• W2798034858 creator A5045967361 @default.
• W2798034858 creator A5051072518 @default.
• W2798034858 creator A5051345685 @default.
• W2798034858 creator A5057555967 @default.
• W2798034858 creator A5064895815 @default.
• W2798034858 date "2018-03-07" @default.
• W2798034858 modified "2023-10-16" @default.
• W2798034858 title "A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase" @default.
• W2798034858 cites W1514966187 @default.
• W2798034858 cites W1964482879 @default.
• W2798034858 cites W1983064104 @default.
• W2798034858 cites W1999101490 @default.
• W2798034858 cites W1999876234 @default.
• W2798034858 cites W2006334733 @default.
• W2798034858 cites W2015008880 @default.
• W2798034858 cites W2016816357 @default.
• W2798034858 cites W2018012729 @default.
• W2798034858 cites W2024072740 @default.
• W2798034858 cites W2035576418 @default.
• W2798034858 cites W2042676899 @default.
• W2798034858 cites W2044098649 @default.
• W2798034858 cites W2069931679 @default.
• W2798034858 cites W2085339035 @default.
• W2798034858 cites W2086186879 @default.
• W2798034858 cites W2088342869 @default.
• W2798034858 cites W2090777221 @default.
• W2798034858 cites W2099196476 @default.
• W2798034858 cites W2101174827 @default.
• W2798034858 cites W2104169873 @default.
• W2798034858 cites W2105689230 @default.
• W2798034858 cites W2109272381 @default.
• W2798034858 cites W2109897538 @default.
• W2798034858 cites W2110726136 @default.
• W2798034858 cites W2112296880 @default.
• W2798034858 cites W2119462367 @default.
• W2798034858 cites W2121017083 @default.
• W2798034858 cites W2130860611 @default.
• W2798034858 cites W2137623277 @default.
• W2798034858 cites W2141125222 @default.
• W2798034858 cites W2144044603 @default.
• W2798034858 cites W2167547775 @default.
• W2798034858 cites W2168062869 @default.
• W2798034858 cites W2172212550 @default.
• W2798034858 cites W2174119068 @default.
• W2798034858 cites W2195303060 @default.
• W2798034858 cites W2287812034 @default.
• W2798034858 cites W2388625588 @default.
• W2798034858 cites W2527755908 @default.
• W2798034858 cites W2533104420 @default.
• W2798034858 cites W2563210283 @default.
• W2798034858 cites W2564594432 @default.
• W2798034858 cites W2587036566 @default.
• W2798034858 cites W2590604244 @default.
• W2798034858 cites W2606955324 @default.
• W2798034858 cites W2613531415 @default.
• W2798034858 cites W2766507491 @default.
• W2798034858 doi "https://doi.org/10.1186/s13045-018-0581-9" @default.
• W2798034858 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5842526" @default.
• W2798034858 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29514683" @default.
• W2798034858 hasPublicationYear "2018" @default.
• W2798034858 type Work @default.
• W2798034858 sameAs 2798034858 @default.
• W2798034858 citedByCount "21" @default.
• W2798034858 countsByYear W27980348582018 @default.
• W2798034858 countsByYear W27980348582019 @default.
• W2798034858 countsByYear W27980348582020 @default.
• W2798034858 countsByYear W27980348582021 @default.
• W2798034858 countsByYear W27980348582022 @default.
• W2798034858 countsByYear W27980348582023 @default.
• W2798034858 crossrefType "journal-article" @default.
• W2798034858 hasAuthorship W2798034858A5003427098 @default.
• W2798034858 hasAuthorship W2798034858A5004994169 @default.
• W2798034858 hasAuthorship W2798034858A5012262880 @default.
• W2798034858 hasAuthorship W2798034858A5035638353 @default.
• W2798034858 hasAuthorship W2798034858A5045967361 @default.
• W2798034858 hasAuthorship W2798034858A5051072518 @default.
• W2798034858 hasAuthorship W2798034858A5051345685 @default.
• W2798034858 hasAuthorship W2798034858A5057555967 @default.
• W2798034858 hasAuthorship W2798034858A5064895815 @default.
• W2798034858 hasBestOaLocation W27980348581 @default.
• W2798034858 hasConcept C137620995 @default.
• W2798034858 hasConcept C185592680 @default.
• W2798034858 hasConcept C30145163 @default.
• W2798034858 hasConcept C502942594 @default.
• W2798034858 hasConcept C62478195 @default.
• W2798034858 hasConcept C75217442 @default.
• W2798034858 hasConcept C86554907 @default.
• W2798034858 hasConcept C86803240 @default.
• W2798034858 hasConcept C95444343 @default.
• W2798034858 hasConceptScore W2798034858C137620995 @default.
• W2798034858 hasConceptScore W2798034858C185592680 @default.
• W2798034858 hasConceptScore W2798034858C30145163 @default.
• W2798034858 hasConceptScore W2798034858C502942594 @default.
• W2798034858 hasConceptScore W2798034858C62478195 @default.

• next