Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients

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dc.citation.firstpage521en_US
dc.citation.journalTitleOncotargeten_US
dc.citation.lastpage533en_US
dc.citation.volumeNumber13en_US
dc.contributor.authorMolina, Eric R.en_US
dc.contributor.authorChim, Letitia K.en_US
dc.contributor.authorLamhamedi-Cherradi, Salah-Eddineen_US
dc.contributor.authorMohiuddin, Sanaen_US
dc.contributor.authorMcCall, Daviden_US
dc.contributor.authorCuglievan, Brankoen_US
dc.contributor.authorKrishnan, Sandhyaen_US
dc.contributor.authorPorter, Robert W.en_US
dc.contributor.authorIngram, Davis R.en_US
dc.contributor.authorWang, Wei-Lienen_US
dc.contributor.authorLazar, Alexander J.en_US
dc.contributor.authorScott, David W.en_US
dc.contributor.authorTruong, Danh D.en_US
dc.contributor.authorDaw, Najat C.en_US
dc.contributor.authorLudwig, Joseph A.en_US
dc.contributor.authorMikos, Antonios G.en_US
dc.date.accessioned2022-04-28T14:29:09Zen_US
dc.date.available2022-04-28T14:29:09Zen_US
dc.date.issued2022en_US
dc.description.abstractOsteosarcoma (OS) is a genetically diverse bone cancer that lacks a consistent targetable mutation. Recent studies suggest the IGF/PI3K/mTOR pathway and YAP/TAZ paralogs regulate cell fate and proliferation in response to biomechanical cues within the tumor microenvironment. How this occurs and their implication upon osteosarcoma survival, remains poorly understood. Here, we show that IGF-1R can translocate into the nucleus, where it may act as part of a transcription factor complex. To explore the relationship between YAP/TAZ and total and nuclear phosphorylated IGF-1R (pIGF-1R), we evaluated sequential tumor sections from a 37-patient tissue microarray by confocal microscopy. Next, we examined the relationship between stained markers, clinical disease characteristics, and patient outcomes. The nuclear to cytoplasmic ratios (N:C ratio) of YAP and TAZ strongly correlated with nuclear pIGF-1R (r = 0.522, p = 0.001 for each pair). Kaplan–Meier analyses indicated that nuclear pIGF-1R predicted poor overall survival, a finding confirmed in the Cox proportional hazards model. Though additional investigation in a larger prospective study will be required to validate the prognostic accuracy of these markers, our results may have broad implications for the new class of YAP, TAZ, AXL, or TEAD inhibitors that have reached early phase clinical trials this year.en_US
dc.identifier.citationMolina, Eric R., Chim, Letitia K., Lamhamedi-Cherradi, Salah-Eddine, et al.. "Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients." <i>Oncotarget,</i> 13, (2022) Oncotarget: 521-533. https://doi.org/10.18632/oncotarget.28215.en_US
dc.identifier.digitaloncotarget-v13-28215en_US
dc.identifier.doihttps://doi.org/10.18632/oncotarget.28215en_US
dc.identifier.urihttps://hdl.handle.net/1911/112190en_US
dc.language.isoengen_US
dc.publisherOncotargeten_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.titleCorrelation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patientsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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