Epithelial cells require contact with extracellular matrix (ECM) to inhibit detachment-induced apoptosis (anoikis). The ERK and PI-3K/Akt signaling pathways have been identified to inhibit anoikis. We present here a different story. An adult rat liver cell line, ARLJ301-3, underwent apoptosis within 4h under suspension conditions even with active forms of Akt and ERK1/2. Once ARLJ301-3 cells are plated on tissue culture plates coated with synthetic polymer. such as poly-(N-p-vinyl benzyl-O-beta-D-galactopyranosyl-D-gluconamide) (PVLA), poly-L-lysine or poly styrene, instead of functional ECM such as fibronectin, they could survive and proliferate without activation of Akt and ERK1/2. The expression of Fas receptor ligand (FasL) are specifically detected in cells under suspension conditions or treated with cytochalasin-D. We present here the first report that FasL expression is up-regulated by the cytoskeletal disruption directed by cytochalasin-D treatment or cell detachment from ECM. (C) 2002 Elsevier Science (USA). All rights reserved.