| Literature DB >> 34358469 |
Shankha Satpathy1, Karsten Krug2, Pierre M Jean Beltran2, Sara R Savage3, Francesca Petralia4, Chandan Kumar-Sinha5, Yongchao Dou3, Boris Reva4, M Harry Kane2, Shayan C Avanessian2, Suhas V Vasaikar6, Azra Krek4, Jonathan T Lei3, Eric J Jaehnig3, Tatiana Omelchenko7, Yifat Geffen2, Erik J Bergstrom2, Vasileios Stathias8, Karen E Christianson2, David I Heiman2, Marcin P Cieslik9, Song Cao10, Xiaoyu Song11, Jiayi Ji11, Wenke Liu12, Kai Li3, Bo Wen3, Yize Li10, Zeynep H Gümüş4, Myvizhi Esai Selvan4, Rama Soundararajan6, Tanvi H Visal6, Maria G Raso6, Edwin Roger Parra6, Özgün Babur13, Pankaj Vats5, Shankara Anand2, Tobias Schraink14, MacIntosh Cornwell14, Fernanda Martins Rodrigues10, Houxiang Zhu10, Chia-Kuei Mo10, Yuping Zhang5, Felipe da Veiga Leprevost5, Chen Huang3, Arul M Chinnaiyan5, Matthew A Wyczalkowski10, Gilbert S Omenn15, Chelsea J Newton16, Stephan Schurer8, Kelly V Ruggles14, David Fenyö12, Scott D Jewell16, Mathangi Thiagarajan17, Mehdi Mesri18, Henry Rodriguez18, Sendurai A Mani6, Namrata D Udeshi2, Gad Getz2, James Suh17, Qing Kay Li19, Galen Hostetter16, Paul K Paik7, Saravana M Dhanasekaran5, Ramaswamy Govindan10, Li Ding10, Ana I Robles18, Karl R Clauser2, Alexey I Nesvizhskii9, Pei Wang4, Steven A Carr20, Bing Zhang21, D R Mani22, Michael A Gillette23.
Abstract
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.Entities:
Keywords: CPTAC; acetylation; genomics; lung cancer; phosphorylation; protein; proteogenomics; proteomics; squamous; ubiquitylation
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Year: 2021 PMID： 34358469 PMCID： PMC8475722 DOI： 10.1016/j.cell.2021.07.016
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850