The Dual Role of Stem Cell-Specific Bcl-2 Function for Epidermal Regeneration and Cancer

The study highlighted the dual role of the anti-apoptotic protein Bcl-2 in epidermal regeneration and cancer. In the context of hair follicle (HF) regeneration, Bcl-2 was crucial for protecting suprabasal bulge stem cells (SCs) from apoptosis, ensuring continued HF renewal. These SCs, located between old and new hair follicles, were particularly reliant on Bcl-2 due to their increased pro-apoptotic signature when cell-matrix adhesion was lost. Conversely, in conditions of oncogenic stress, Bcl-2 expression was reduced in the SC compartment but elevated in tumors, suggesting that Bcl-2 facilitated the survival and selection of SCs that could lead to tumor formation. The study used a mutant Lef1 mouse model to demonstrate that overexpression of Bcl-2 increased tumor incidence and frequency, indicating its role in promoting tumorigenesis.