Wounding triggers invasive progression in human basal cell carcinoma

Abstract The interconnection between wound healing and cancer has long been recognized, as epitomized by the expression “cancer is a wound that does not heal”. However, the impact of inducing a wound, such as through biopsy collection, on the progression of established tumors remains largely unknown. In this study, we apply single-cell spatial transcriptomics to characterize the heterogeneity of human basal cell carcinoma (BCC) and identify a wound response gene program as the most prominent feature of highly invasive BCC. To explore the causal relationship between wounding and cancer invasive progression, we perform a longitudinal experiment to compare human tumors at baseline and one week post-biopsy. Our results demonstrate that biopsy collection triggers, in proximity of the wound, the same transcriptional cancer cell state observed in highly invasive BCC. This cancer cell transcriptional switch is coupled with morphological changes and the transcriptional reprogramming of cancer-associated fibroblasts (CAFs). This study provides evidence that wounding triggers invasive progression of established human tumors and warrants further research on the potentially harmful effects of biopsies and wound-inducing treatments.