A proteogenomic portrait of lung squamous cell carcinoma.

A proteogenomic portrait of lung squamous cell carcinoma.

Cell (2021-08-07)

Shankha Satpathy, Karsten Krug, Pierre M Jean Beltran, Sara R Savage, Francesca Petralia, Chandan Kumar-Sinha, Yongchao Dou, Boris Reva, M Harry Kane, Shayan C Avanessian, Suhas V Vasaikar, Azra Krek, Jonathan T Lei, Eric J Jaehnig, Tatiana Omelchenko, Yifat Geffen, Erik J Bergstrom, Vasileios Stathias, Karen E Christianson, David I Heiman, Marcin P Cieslik, Song Cao, Xiaoyu Song, Jiayi Ji, Wenke Liu, Kai Li, Bo Wen, Yize Li, Zeynep H Gümüş, Myvizhi Esai Selvan, Rama Soundararajan, Tanvi H Visal, Maria G Raso, Edwin Roger Parra, Özgün Babur, Pankaj Vats, Shankara Anand, Tobias Schraink, MacIntosh Cornwell, Fernanda Martins Rodrigues, Houxiang Zhu, Chia-Kuei Mo, Yuping Zhang, Felipe da Veiga Leprevost, Chen Huang, Arul M Chinnaiyan, Matthew A Wyczalkowski, Gilbert S Omenn, Chelsea J Newton, Stephan Schurer, Kelly V Ruggles, David Fenyö, Scott D Jewell, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Sendurai A Mani, Namrata D Udeshi, Gad Getz, James Suh, Qing Kay Li, Galen Hostetter, Paul K Paik, Saravana M Dhanasekaran, Ramaswamy Govindan, Li Ding, Ana I Robles, Karl R Clauser, Alexey I Nesvizhskii, Pei Wang, Steven A Carr, Bing Zhang, D R Mani, Michael A Gillette

PMID34358469

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.

MATERIALS

Product Number

Brand

Product Description

HPA051235

Sigma-Aldrich

Anti-ARHGDIB antibody produced in rabbit, Prestige Antibodies^® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution