Anoikis - apoptotic cell death triggered by loss of extracellular matrix (ECM) 
contacts - is dysregulated in many chronic debilitating and fatal diseases. 
Mechanisms rendering tumor cells resistant to anoikis, although not completely 
understood, possess significant therapeutic promise. In death receptor-mediated 
anoikis mechanisms, focal adhesion kinase (FAK) and receptor-interacting protein 
(RIP) dissociate, leading to association of RIP with Fas, formation of the 
death-inducing signaling complex (DISC), activation of caspase-3, and 
propagation of anoikis. In contrast, anoikis resistance is accomplished through 
constitutive activation of survival pathways that include integrin-dependent 
activation of FAK and extracellular-signal-regulated kinase (ERK). In addition, 
FAK and RIP association confers anoikis resistance by inhibiting the association 
of RIP with Fas and formation of the death signaling complex, which allows cells 
to escape anoikis. Up-regulation of CD44 also contributes to survival signals 
and promotes anoikis resistance. This review will focus on the roles of death 
receptors, prosurvival pathways, and the molecular players involved in anoikis 
escalation and resistance in oral squamous cell carcinoma.