Switch from alphavbeta5 to alphavbeta6 integrin expression protects squamous cell carcinomas from anoikis

Area of Science:

• Cell Biology
• Integrin Signaling
• Cancer Research

Background:

• Stratified squamous epithelia normally express alphavbeta5 integrin.
• Squamous cell carcinomas (SCCs) show decreased alphavbeta5 and increased alphavbeta6 integrin expression.
• Integrin expression changes in cancer may impact cell survival.

Purpose of the Study:

• To investigate the functional significance of altered alphavbeta5 and alphavbeta6 integrin expression in SCCs.
• To determine the role of integrins in anoikis (apoptosis induced by suspension) in SCCs.
• To elucidate the signaling pathways involved in integrin-mediated anoikis resistance.

Main Methods:

• Transduction of an alphav-negative human SCC cell line with retroviral vectors encoding alphavbeta5 or alphavbeta6 integrins.
• Assessment of anoikis in engineered SCC cells under suspension culture conditions.
• Analysis of protein kinase B/Akt (PKB/Akt) activation, phosphatidylinositol 3-kinase (PI3K) levels, and caspase activity.

Main Results:

• Cells expressing alphavbeta5 underwent anoikis, while alphav-negative and alphavbeta6-expressing cells resisted anoikis.
• Resistance to anoikis correlated with PKB/Akt activation in suspension.
• Inhibition of PI3K induced anoikis, while Akt activation or caspase inhibition suppressed anoikis in alphavbeta5-expressing cells.

Conclusions:

• Down-regulation of alphavbeta5 integrin and up-regulation of alphavbeta6 integrin may confer resistance to anoikis in SCCs.
• Activation of a PKB/Akt survival pathway is implicated in anoikis resistance mediated by integrin changes.
• These findings suggest a mechanism by which SCCs evade apoptosis, potentially promoting tumor progression.