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Anoikis mediators in oral squamous cell carcinoma
Author(s) -
Bunek J,
Kamarajan P,
Kapila YL
Publication year - 2011
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/j.1601-0825.2010.01763.x
Subject(s) - anoikis , programmed cell death , focal adhesion , mapk/erk pathway , cancer research , microbiology and biotechnology , signal transduction , extracellular matrix , kinase , integrin , apoptosis , biology , cell , biochemistry
Oral Diseases (2011) 17 , 355–361 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.