Trending With Impact: Cancer-Related Pathways Linked in Osteosarcoma

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Oncotarget

Oncotarget published this trending research paper on March 9, 2022 in Volume 13, entitled, "Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients" by researchers from the Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX; Department of Bioengineering, Rice University, Houston, TX; Division of Pediatrics, The University of Texas, MD Anderson Cancer Center, Houston, TX; Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX; Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX; Department of Statistics, Rice University, Houston, TX. DOI - https://doi.org/10.18632/oncotarget.28215 Correspondence to - Joseph A. Ludwig - jaludwig@mdanderson.org, and Antonios G. Mikos - mikos@rice.edu Abstract Osteosarcoma (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. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28215 Keywords - osteosarcoma, YAP/TAZ, IGF-1R, nuclear IGF-1R, mechanotransduction About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957