Article highlights & insights
Tractable, patient-relevant models are needed to investigate cancer progression and heterogeneity. Here, Dr Lopez-Garcia and his group report an alternative in vitro model of lung squamous cell carcinoma (LUSC) using primary human bronchial epithelial cells (hBECs) from three healthy donors. The co-operation of ubiquitous alterations (TP53 and CDKN2A loss) and components of commonly deregulated pathways including squamous differentiation (SOX2), PI3K signalling (PTEN) and the oxidative stress response (KEAP1) is investigated by generating hBECs harbouring cumulative alterations.
The group’s analyses confirms that SOX2-overexpression initiates early preinvasive LUSC stages, and co-operation with the oxidative stress response and PI3K pathways to drive more aggressive phenotypes, with expansion of cells expressing LUSC biomarkers and invasive properties. This cooperation is consistent with the classical LUSC subtype. Importantly, they connect pathway dysregulation with gene expression changes associated with cell-intrinsic processes and immunomodulation. Their approach constitutes a powerful system to model LUSC and unravel genotype-phenotype causations of clinical relevance.
Tractable, patient-relevant models are needed to investigate cancer progression and heterogeneity. Here, Dr Lopez-Garcia and his group report an alternative in vitro model of lung squamous cell carcinoma (LUSC) using primary human bronchial epithelial cells (hBECs) from three healthy donors. The co-operation of ubiquitous alterations (TP53 and CDKN2A loss) and components of commonly deregulated pathways including squamous differentiation (SOX2), PI3K signalling (PTEN) and the oxidative stress response (KEAP1) is investigated by generating hBECs harbouring cumulative alterations.
The group’s analyses confirms that SOX2-overexpression initiates early preinvasive LUSC stages, and co-operation with the oxidative stress response and PI3K pathways to drive more aggressive phenotypes, with expansion of cells expressing LUSC biomarkers and invasive properties. This cooperation is consistent with the classical LUSC subtype. Importantly, they connect pathway dysregulation with gene expression changes associated with cell-intrinsic processes and immunomodulation. Their approach constitutes a powerful system to model LUSC and unravel genotype-phenotype causations of clinical relevance.