Anoikis mediators in oral squamous cell carcinoma.
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.
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
J
J
Bunek
P
P
Kamarajan
Y L
YL
Kapila
D023102:Anoikis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D053148:Caspase 3 / Q000502:physiology; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D009062:Mouth Neoplasms / Q000503:physiopathology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
C497483:CD44 protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; D018960:Hyaluronan Receptors; D019014:fas Receptor; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053148:Caspase 3