The idea that proteins or signalling pathways could have both positive and negative effects on tumour progression might seem rather surprising, but is a common theme in this issue.

On page 807, Peter Siegel and Joan Massagué describe how the TGF-β signalling pathway can both inhibit early stages of tumour development, by activating the apoptotic and cytostatic programmes, and promote the late stages of tumour progression, by inducing angiogenesis and metastasis. One of the key remaining questions was what determined the response to TGF-β — was it the cell type, defining lesions or simply a matter of disease stage? The answer seems to be the last alternative, as discussed in a highlight on page 805.

The AP-1 transcription factor is another example of a protein complex that can promote and inhibit tumour growth. Although originally thought to be oncogenic — as two of the proteins that form the dimeric complex, JUN and FOS, are homologous to viral oncogenes — AP-1 has more recently been found to act as a tumour suppressor. This choice depends on the composition of AP-1 and the cellular context.

Finally, the tumour suppressor merlin belongs to the protein 4.1 superfamily, which also contains ezrin, radixin and moesin (ERM). These four proteins share similarities in subcellular localization and binding partners, as well as the ability to interact with each other, but does the similarity end here? Andrea McClatchey discusses on page 877 that merlin and the ERM proteins might have antagonistic roles in tumour development, as the ERMs can promote proliferation and metastasis.

Although cancer pathways are getting ever more complicated, we are slowly uncovering their secrets and should soon be able to use this knowledge against the developing tumours.