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Molecular Cancer
Published in: Molecular Cancer 1/2023

Open Access 01-12-2023 | Research

USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity

Authors: Juntae Kwon, Jinmin Zhang, Boram Mok, Samuel Allsup, Chul Kim, Jeffrey Toretsky, Cecil Han

Published in: Molecular Cancer | Issue 1/2023

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Abstract

Lung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, yet its role in lung cancer is largely unknown. Here, we established a novel mouse model of LUSC by overexpressing USP13 on KrasG12D/+; Trp53flox/flox background (KPU). KPU-driven lung squamous tumors faithfully recapitulate key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells of the airway and reinforced the fate of club cells to squamous carcinoma development. We showed a strong molecular association between USP13 and c-MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate that USP13 is a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of LUSC.

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Metadata
Title
USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity
Authors
Juntae Kwon
Jinmin Zhang
Boram Mok
Samuel Allsup
Chul Kim
Jeffrey Toretsky
Cecil Han
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2023
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-023-01892-x

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