Addition of an integrin (right) prevents anchorage-independent growth.

Most cells undergo a form of apoptosis called anoikis when they are grown in suspension. Janes and Watt report on page 419 that squamous cell carcinomas (SCCs) avoid this fate by expressing an alternative integrin called αvβ6. The pathway may be appropriated from cells that require a temporary reprieve from substrate-dependent growth during differentiation or tissue repair.

The αvβ6 integrin is known to favor tumor formation by increasing cell invasion and proliferation and inhibiting matrix assembly, but the new study is the first to demonstrate its ability to confer a survival advantage. The authors introduced αv into an αv-null cell line and showed that suspended transfectants died because their αvβ5 acted via caspase 8 to suppress activation of an Akt survival signal. Addition of both αv and β6, however, resulted in formation of αvβ6, which supported Akt activation and survival.

Squamous epithelial cells start off life attached to a basement membrane, but when they detach and move upwards into suprabasal layers, the Akt survival signal may give them sufficient time to respond to differentiation cues. The expression of αvβ6, as occurs in repairing and proliferating tissues, may extend this survival benefit under special conditions. Normally, αvβ6's reprieve is temporary, but tumors appear to switch on αvβ6 more robustly and thus make the condition of substrate-independent growth permanent. ▪