Apoptosis and proliferation are two dynamically and tightly regulated processes 
that together maintain the homeostasis of renewable tissues. Anoikis is a 
subtype of apoptosis induced by detachment of adherent cells from the 
extracellular matrix. By using the defined mTeSR1 medium and collecting freshly 
detached cells, we found here that human pluripotent stem (PS) cells including 
embryonic stem (ES) cells and induced pluripotent stem cells are subject to 
constant anoikis in culture, which is escalated in the absence of basic 
fibroblast growth factor (bFGF). Withdrawal of bFGF also promotes apoptosis and 
differentiation of the remaining adherent cells without affecting their cell 
cycle progression. Insulin-like growth factor 2 (IGF2) has previously been 
reported to act downstream of FGF signaling to support self-renewal of human ES 
cells. However, we found that IGF2 cannot substitute bFGF in the TeSR1-supported 
culture, although endogenous IGF signaling is required to sustain self-renewal 
of human ES cells. On the other hand, all of the bFGF withdrawal effects 
observed here can be markedly prevented by the caspase inhibitor z-VAD-FMK. We 
further demonstrated that the bFGF-repressed anoikis is dependent on activation 
of ERK and AKT and associated with inhibition of Bcl-2-interacting mediator of 
cell death and the caspase-ROCK1-myosin signaling. Anoikis is independent of 
pre-detachment apoptosis and differentiation of the cells. Because previous 
studies of human PS cells have been focused on attached cells, our findings 
revealed a neglected role of bFGF in sustaining self-renewal of human PS cells: 
preventing them from anoikis via inhibition of caspase activation.