Wounding triggers invasive progression in human basal cell carcinoma

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 those from biopsies, on the progression of established tumors remains largely unknown. In this study, we examine the transcriptional heterogeneity of cancer cells in human basal cell carcinoma (BCC) and identify a wound response-associated gene program as a prominent feature of invasive cancer cells. We find that invasive cancer cells are prevalent in ulcerated BCC tumors and exhibit a distinctive spatial organization. To explore the causal relationship between wounding and cancer progression, we compare tumors at baseline and one week after biopsy. Our results reveal that biopsy collection locally induces a transcriptional switch in cancer cells from an indolent to an invasive state. Notably, this progression is coupled with the reprogramming of cancer-associated fibroblasts, which adopt a transcriptional state characteristic of therapy-resistant BCC. 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.