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dc.contributor.authorSchaus, Scotten_US
dc.contributor.authorHansen, Ullaen_US
dc.contributor.authorWilloughby, Jennifer L. S.en_US
dc.contributor.authorGeorge, Kellyen_US
dc.contributor.authorRoberto, Mark P.en_US
dc.contributor.authorChin, Hang Gyeongen_US
dc.contributor.authorStoiber, Patricken_US
dc.contributor.authorShin, Hyunjinen_US
dc.contributor.authorPedamallu, Chandra Sekharen_US
dc.contributor.authorFitzgerald, Kevinen_US
dc.contributor.authorShah, Jageshen_US
dc.date.accessioned2020-05-04T15:57:30Z
dc.date.available2020-05-04T15:57:30Z
dc.identifierhttps://www.biorxiv.org/content/10.1101/665570v1
dc.identifier.citationScott Schaus, Ulla Hansen, Jennifer LS Willoughby, Kelly George, Mark P Roberto, Hang Gyeong Chin, Patrick Stoiber, Hyunjin Shin, Chandra Sekhar Pedamallu, Kevin Fitzgerald, Jagesh Shah. "LSF small molecule inhibitors phenocopy LSF-targeted siRNAs causing mitotic defects and senescence in cancer cells." https://doi.org/10.1101/665570
dc.identifier.urihttps://hdl.handle.net/2144/40536
dc.description.abstractThe oncogene LSF has been proposed as a novel target with therapeutic potential for multiple cancers. LSF overexpression correlates with poor prognosis for both liver and colorectal cancers, for which there are currently limited therapeutic treatment options. In particular, molecularly targeted therapies for hepatocellular carcinoma targeting cellular receptors and kinases have yielded disappointing clinical results, providing an urgency for targeting distinct mechanisms. LSF small molecule inhibitors, Factor Quinolinone Inhibitors (FQIs), have exhibited robust anti-tumor activity in multiple pre-clinical models of hepatocellular carcinoma, with no observable toxicity. To understand how the inhibitors impact cancer cell proliferation, we characterized the cellular phenotypes that result from loss of LSF activity. Phenotypically, inhibition of LSF activity induced a mitotic delay with condensed, but unaligned, chromosomes. This mitotic disruption resulted in improper cellular division leading to multiple outcomes: multi-nucleation, apoptosis, and cellular senescence. The cellular phenotypes observed upon FQI1 treatment were due specifically to the loss of LSF activity, as siRNA specifically targeting LSF produced nearly identical phenotypes. Taken together, these findings confirm that LSF is a promising therapeutic target for cancer treatment.en_US
dc.language.isoen_US
dc.publisherbioRxiven_US
dc.rightsThe copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.en_US
dc.rights© 2018 ARVO. This work is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLSFen_US
dc.subjectFQI1en_US
dc.subjectsiRNAen_US
dc.subjectMitosisen_US
dc.subjectSenescenceen_US
dc.titleLSF small molecule inhibitors phenocopy LSF-targeted siRNAs causing mitotic defects and senescence in cancer cellsen_US
dc.typeOtheren_US
dc.description.versionFirst author draften_US
dc.identifier.doi10.1101/665570
pubs.elements-sourcemanual-entryen_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
dc.date.online2019-06-11
dc.identifier.mycv529090


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The copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.