PRF1 and neoplasm: Perforin initiates the killing cascade by forming pores in the target cell membrane, which activates the membrane repair response, leading to the uptake of granzymes into the target cell cytoplasm, where they cleave many key substrates to trigger cell apoptosis.343 However, tumor cells can soften their cell membranes by diminishing their cytoskeletal framework18,19 or by reducing the cholesterol content within their cell membranes,227 thereby diminishing the pore-forming efficacy of perforin.