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The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling

Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with an extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of the tumor epithelial compartment has remained a mystery....

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Autores principales: Tay, Joshua K., Zhu, Chunfang, Shin, June Ho, Zhu, Shirley X., Varma, Sushama, Foley, Joseph W., Vennam, Sujay, Yip, Yim Ling, Goh, Chuan Keng, Wang, De Yun, Loh, Kwok Seng, Tsao, Sai Wah, Le, Quynh-Thu, Sunwoo, John B., West, Robert B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993121/
https://www.ncbi.nlm.nih.gov/pubmed/35394843
http://dx.doi.org/10.1126/sciadv.abh2445
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author Tay, Joshua K.
Zhu, Chunfang
Shin, June Ho
Zhu, Shirley X.
Varma, Sushama
Foley, Joseph W.
Vennam, Sujay
Yip, Yim Ling
Goh, Chuan Keng
Wang, De Yun
Loh, Kwok Seng
Tsao, Sai Wah
Le, Quynh-Thu
Sunwoo, John B.
West, Robert B.
author_facet Tay, Joshua K.
Zhu, Chunfang
Shin, June Ho
Zhu, Shirley X.
Varma, Sushama
Foley, Joseph W.
Vennam, Sujay
Yip, Yim Ling
Goh, Chuan Keng
Wang, De Yun
Loh, Kwok Seng
Tsao, Sai Wah
Le, Quynh-Thu
Sunwoo, John B.
West, Robert B.
author_sort Tay, Joshua K.
collection PubMed
description Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with an extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of the tumor epithelial compartment has remained a mystery. Here, we use Smart-3SEQ to prepare transcriptome-wide gene expression profiles from microdissected NPC tumors, dysplasia, and normal controls. We describe changes in biological pathways across the normal to tumor spectrum and show that fibroblast growth factor (FGF) ligands are overexpressed in NPC tumors, while negative regulators of FGF signaling, including SPRY1, SPRY2, and LGALS3, are down-regulated early in carcinogenesis. Within the NF-κB signaling pathway, the critical noncanonical transcription factors, RELB and NFKB2, are enriched in the majority of NPC tumors. We confirm the responsiveness of EBV-positive NPC cell lines to targeted inhibition of these pathways, reflecting the heterogeneity in NPC patient tumors. Our data comprehensively describe the gene expression landscape of NPC and unravel the mysteries of receptor tyrosine kinase and NF-κB pathways in NPC.
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spelling pubmed-89931212022-04-22 The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling Tay, Joshua K. Zhu, Chunfang Shin, June Ho Zhu, Shirley X. Varma, Sushama Foley, Joseph W. Vennam, Sujay Yip, Yim Ling Goh, Chuan Keng Wang, De Yun Loh, Kwok Seng Tsao, Sai Wah Le, Quynh-Thu Sunwoo, John B. West, Robert B. Sci Adv Biomedicine and Life Sciences Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with an extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of the tumor epithelial compartment has remained a mystery. Here, we use Smart-3SEQ to prepare transcriptome-wide gene expression profiles from microdissected NPC tumors, dysplasia, and normal controls. We describe changes in biological pathways across the normal to tumor spectrum and show that fibroblast growth factor (FGF) ligands are overexpressed in NPC tumors, while negative regulators of FGF signaling, including SPRY1, SPRY2, and LGALS3, are down-regulated early in carcinogenesis. Within the NF-κB signaling pathway, the critical noncanonical transcription factors, RELB and NFKB2, are enriched in the majority of NPC tumors. We confirm the responsiveness of EBV-positive NPC cell lines to targeted inhibition of these pathways, reflecting the heterogeneity in NPC patient tumors. Our data comprehensively describe the gene expression landscape of NPC and unravel the mysteries of receptor tyrosine kinase and NF-κB pathways in NPC. American Association for the Advancement of Science 2022-04-08 /pmc/articles/PMC8993121/ /pubmed/35394843 http://dx.doi.org/10.1126/sciadv.abh2445 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Tay, Joshua K.
Zhu, Chunfang
Shin, June Ho
Zhu, Shirley X.
Varma, Sushama
Foley, Joseph W.
Vennam, Sujay
Yip, Yim Ling
Goh, Chuan Keng
Wang, De Yun
Loh, Kwok Seng
Tsao, Sai Wah
Le, Quynh-Thu
Sunwoo, John B.
West, Robert B.
The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title_full The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title_fullStr The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title_full_unstemmed The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title_short The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling
title_sort microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in fgf and noncanonical nf-κb signaling
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993121/
https://www.ncbi.nlm.nih.gov/pubmed/35394843
http://dx.doi.org/10.1126/sciadv.abh2445
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