We know that close attachments between animals can help them survive difficult times, and attachments are also important for cell survival. If a cell becomes detached from the extracellular matrix, it undergoes apoptosis — a process known as anoikis. And, in Cell, Ruoslahti and colleagues now describe an integrin-regulated pathway that is, at least partly, responsible for the cell-survival effects of such attachments.

They first identified a pro-apoptotic protein, BIT1, which localizes to mitochondria, and they showed that cytoplasmic expression of BIT1 induces apoptosis. In addition, they showed that cytoplasmic BIT1 can form a complex with cytoplasmic AES (a protein of the Groucho transcriptional-corepressor family), and that BIT1 and AES work together to induce apoptosis in a caspase-independent manner.

Next the authors showed that cells that bound to fibronectin through the α5β1 integrin were protected against BIT1/AES-induced apoptosis: this integrin seems to produce signals that block this apoptosis. Furthermore, they found that reducing BIT1 expression in detached cells promoted cell survival, whereas increasing BIT1 expression promoted cell death.

In the final part of this study, Ruoslahti and co-workers showed that another Groucho-family protein — the anti-apoptotic protein TLE1 — can inhibit BIT1/AES-induced apoptosis by interfering with BIT1–AES-complex formation. They therefore propose a model in which cell detachment somehow induces the release of BIT1 from mitochondria, which promotes the formation of BIT1–AES complexes. They suggest that these complexes might then switch off a gene-transcription programme that promotes cell survival. Although the molecular details of this pathway need to be further clarified, this study has identified BIT1 as a potential “...guardian of anchorage dependence”.