FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2519134577> ?p ?o ?g. }

• W2519134577 endingPage "6700" @default.
• W2519134577 startingPage "6690" @default.
• W2519134577 abstract "Abstract Centrosome amplification is a hallmark of virtually all types of cancers, including solid tumors and hematologic malignancies. Cancer cells with extra centrosomes use centrosome clustering (CC) to allow for successful division. Because normal cells do not rely on this mechanism, CC is regarded as a promising target to selectively eradicate cells harboring supernumerary centrosomes. To identify novel inhibitors of CC, we developed a cell-based high-throughput screen that reports differential drug cytotoxicity for isogenic cell populations with different centrosome contents. We identified CP-673451 and crenolanib, two chemically related compounds originally developed for the inhibition of platelet-derived growth factor receptor β (PDGFR-β), as robust inhibitors of CC with selective cytotoxicity for cells with extra centrosomes. We demonstrate that these compounds induce mitotic spindle multipolarity by activation of the actin-severing protein cofilin, leading to destabilization of the cortical actin network, and provide evidence that this activation is dependent on slingshot phosphatases 1 and 2 but unrelated to PDGFR-β inhibition. More specifically, we found that although both compounds attenuated PDGF-BB–induced signaling, they significantly enhanced the phosphorylation of PDGFR-β downstream effectors, Akt and MEK, in almost all tested cancer cell lines under physiologic conditions. In summary, our data reveal a novel mechanism of CC inhibition depending on cofilin-mediated cortical actin destabilization and identify two clinically relevant compounds interfering with this tumor cell–specific target. Cancer Res; 76(22); 6690–700. ©2016 AACR." @default.
• W2519134577 created "2016-09-23" @default.
• W2519134577 creator A5003401873 @default.
• W2519134577 creator A5024363113 @default.
• W2519134577 creator A5029575769 @default.
• W2519134577 creator A5063868618 @default.
• W2519134577 creator A5066882189 @default.
• W2519134577 creator A5070221339 @default.
• W2519134577 creator A5074750592 @default.
• W2519134577 creator A5077972762 @default.
• W2519134577 creator A5078452627 @default.
• W2519134577 creator A5087064238 @default.
• W2519134577 date "2016-11-14" @default.
• W2519134577 modified "2023-10-17" @default.
• W2519134577 title "Pharmacological Inhibition of Centrosome Clustering by Slingshot-Mediated Cofilin Activation and Actin Cortex Destabilization" @default.
• W2519134577 cites W1484094963 @default.
• W2519134577 cites W1640813462 @default.
• W2519134577 cites W1882824745 @default.
• W2519134577 cites W1947936721 @default.
• W2519134577 cites W1963759286 @default.
• W2519134577 cites W1971204916 @default.
• W2519134577 cites W1971579914 @default.
• W2519134577 cites W1977721021 @default.
• W2519134577 cites W1984712646 @default.
• W2519134577 cites W1985646870 @default.
• W2519134577 cites W1987411178 @default.
• W2519134577 cites W1989139022 @default.
• W2519134577 cites W1991033145 @default.
• W2519134577 cites W1993475190 @default.
• W2519134577 cites W1993881193 @default.
• W2519134577 cites W1994265469 @default.
• W2519134577 cites W2005073257 @default.
• W2519134577 cites W2005218158 @default.
• W2519134577 cites W2022726449 @default.
• W2519134577 cites W2025829112 @default.
• W2519134577 cites W2028497798 @default.
• W2519134577 cites W2030777833 @default.
• W2519134577 cites W2033654911 @default.
• W2519134577 cites W2042288505 @default.
• W2519134577 cites W2044798778 @default.
• W2519134577 cites W2048718074 @default.
• W2519134577 cites W2058620622 @default.
• W2519134577 cites W2072895299 @default.
• W2519134577 cites W2076491926 @default.
• W2519134577 cites W2079117904 @default.
• W2519134577 cites W2092002157 @default.
• W2519134577 cites W2101452250 @default.
• W2519134577 cites W2102659321 @default.
• W2519134577 cites W2111005916 @default.
• W2519134577 cites W2112380414 @default.
• W2519134577 cites W2114610097 @default.
• W2519134577 cites W2126546276 @default.
• W2519134577 cites W2128126810 @default.
• W2519134577 cites W2134590240 @default.
• W2519134577 cites W2144779659 @default.
• W2519134577 cites W2148309012 @default.
• W2519134577 cites W2151172815 @default.
• W2519134577 cites W2151258061 @default.
• W2519134577 cites W2153218395 @default.
• W2519134577 cites W2156393663 @default.
• W2519134577 cites W2162024486 @default.
• W2519134577 cites W2189225177 @default.
• W2519134577 cites W2253467674 @default.
• W2519134577 doi "https://doi.org/10.1158/0008-5472.can-16-1144" @default.
• W2519134577 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27634760" @default.
• W2519134577 hasPublicationYear "2016" @default.
• W2519134577 type Work @default.
• W2519134577 sameAs 2519134577 @default.
• W2519134577 citedByCount "23" @default.
• W2519134577 countsByYear W25191345772017 @default.
• W2519134577 countsByYear W25191345772018 @default.
• W2519134577 countsByYear W25191345772019 @default.
• W2519134577 countsByYear W25191345772020 @default.
• W2519134577 countsByYear W25191345772021 @default.
• W2519134577 countsByYear W25191345772022 @default.
• W2519134577 countsByYear W25191345772023 @default.
• W2519134577 crossrefType "journal-article" @default.
• W2519134577 hasAuthorship W2519134577A5003401873 @default.
• W2519134577 hasAuthorship W2519134577A5024363113 @default.
• W2519134577 hasAuthorship W2519134577A5029575769 @default.
• W2519134577 hasAuthorship W2519134577A5063868618 @default.
• W2519134577 hasAuthorship W2519134577A5066882189 @default.
• W2519134577 hasAuthorship W2519134577A5070221339 @default.
• W2519134577 hasAuthorship W2519134577A5074750592 @default.
• W2519134577 hasAuthorship W2519134577A5077972762 @default.
• W2519134577 hasAuthorship W2519134577A5078452627 @default.
• W2519134577 hasAuthorship W2519134577A5087064238 @default.
• W2519134577 hasConcept C10447061 @default.
• W2519134577 hasConcept C121608353 @default.
• W2519134577 hasConcept C142669718 @default.
• W2519134577 hasConcept C1491633281 @default.
• W2519134577 hasConcept C185592680 @default.
• W2519134577 hasConcept C2776601116 @default.
• W2519134577 hasConcept C29537977 @default.
• W2519134577 hasConcept C2993400109 @default.
• W2519134577 hasConcept C502942594 @default.
• W2519134577 hasConcept C54355233 @default.
• W2519134577 hasConcept C55493867 @default.

• next