Plakophilins 1-3 are members of the p120(ctn)-family of armadillo related
proteins. They have been characterized as desmosomal plaque
proteins, stabilizing
desmosomal cadherins at the plasma membrane and interacting with the cytoskeletal linker
protein desmoplakin. Loss of cell adhesion contributes to cancerogenesis. In agreement with this, some
tumors were found to lack
plakophilin expression. Surprisingly, in other
tumors,
plakophilins 1 and 3 are overexpressed. We have recently identified a function of
plakophilins 1 and 3 in the regulation of
protein synthesis.
Plakophilin 1 was characterized as a component of the cap-binding translation initiation complex where it associates directly with the
initiation factor eIF4A1.
Plakophilin 1 not only stimulated the recruitment of eIF4A1 into the cap complex but also its helicase activity. This pointed to a role of
plakophilin 1 in the stimulation of proliferation. Given the importance of mRNA translation and
protein synthesis in the development of
cancer, we speculate that overexpressed
plakophilin 1 could contribute to
tumor formation. Thus,
plakophilin's function in cancerogenesis could go both ways: while an increase of
plakophilin could support cancerogenesis via the stimulation of translation and proliferation, loss of
plakophilin could contribute to cancerogenesis and/or
metastasis via loss of contact inhibition and increased motility. Elucidating the regulation of
plakophilin's function in adhesion versus translation will help to understand this context-dependent phenomenon.