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

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 thei...

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Autores principales: Molina, Eric R., Chim, Letitia K., Lamhamedi-Cherradi, Salah-Eddine, Mohiuddin, Sana, McCall, David, Cuglievan, Branko, Krishnan, Sandhya, Porter, Robert W., Ingram, Davis R., Wang, Wei-Lien, Lazar, Alexander J., Scott, David W., Truong, Danh D., Daw, Najat C., Ludwig, Joseph A., Mikos, Antonios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906536/
https://www.ncbi.nlm.nih.gov/pubmed/35284040
http://dx.doi.org/10.18632/oncotarget.28215
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author Molina, Eric R.
Chim, Letitia K.
Lamhamedi-Cherradi, Salah-Eddine
Mohiuddin, Sana
McCall, David
Cuglievan, Branko
Krishnan, Sandhya
Porter, Robert W.
Ingram, Davis R.
Wang, Wei-Lien
Lazar, Alexander J.
Scott, David W.
Truong, Danh D.
Daw, Najat C.
Ludwig, Joseph A.
Mikos, Antonios G.
author_facet Molina, Eric R.
Chim, Letitia K.
Lamhamedi-Cherradi, Salah-Eddine
Mohiuddin, Sana
McCall, David
Cuglievan, Branko
Krishnan, Sandhya
Porter, Robert W.
Ingram, Davis R.
Wang, Wei-Lien
Lazar, Alexander J.
Scott, David W.
Truong, Danh D.
Daw, Najat C.
Ludwig, Joseph A.
Mikos, Antonios G.
author_sort Molina, Eric R.
collection PubMed
description 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.
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spelling pubmed-89065362022-03-10 Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients Molina, Eric R. Chim, Letitia K. Lamhamedi-Cherradi, Salah-Eddine Mohiuddin, Sana McCall, David Cuglievan, Branko Krishnan, Sandhya Porter, Robert W. Ingram, Davis R. Wang, Wei-Lien Lazar, Alexander J. Scott, David W. Truong, Danh D. Daw, Najat C. Ludwig, Joseph A. Mikos, Antonios G. Oncotarget Research Paper 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. Impact Journals LLC 2022-03-09 /pmc/articles/PMC8906536/ /pubmed/35284040 http://dx.doi.org/10.18632/oncotarget.28215 Text en Copyright: © 2022 Molina et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Molina, Eric R.
Chim, Letitia K.
Lamhamedi-Cherradi, Salah-Eddine
Mohiuddin, Sana
McCall, David
Cuglievan, Branko
Krishnan, Sandhya
Porter, Robert W.
Ingram, Davis R.
Wang, Wei-Lien
Lazar, Alexander J.
Scott, David W.
Truong, Danh D.
Daw, Najat C.
Ludwig, Joseph A.
Mikos, Antonios G.
Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title_full Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title_fullStr Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title_full_unstemmed Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title_short Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients
title_sort correlation of nuclear pigf-1r/igf-1r and yap/taz in a tissue microarray with outcomes in osteosarcoma patients
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906536/
https://www.ncbi.nlm.nih.gov/pubmed/35284040
http://dx.doi.org/10.18632/oncotarget.28215
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