Airway basal cells are the cells of origin for lung squamous cell carcinoma (LUSC). Normally, they undergo neutral competition and maintain epithelial integrity through balanced self-renewal and differentiation. Carcinogen induced alterations disrupt this and confer fitness advantages that enable specific basal cell clones to outcompete neighbours and expand across the airway – a prerequisite for LUSC development. Defining these early events is critical for predicting and intercepting LUSC. TP53 loss is postulated to drive aberrant basal cell clonal expansion in vivo; however, these early dynamics have not been modelled in vitro.
Matsumoto et al. (Tue,) studied this question.