Transmembrane peptides as inhibitors of protein-protein interactions: an efficient strategy to target cancer cells?

Frontiers in Oncology. 2020. Vol. 10. P. 519.

Efremov R., Albrecht C., Appert-Collin A., Bagnard D., Sébastien B., Romier-Crouzet B., Sartelet H., Duca L., Maurice P., Bennasroune A.

Cellular functions are regulated by extracellular signals such as hormones,
neurotransmitters, matrix ligands, and other chemical or physical stimuli. Ligand
binding on its transmembrane receptor induced cell signaling and the recruitment of
several interacting partners to the plasma membrane. Nowadays, it is well-established
that the transmembrane domain is not only an anchor of these receptors to the
membrane, but it also plays a key role in receptor dimerization and activation. Indeed,
interactions between transmembrane helices are associated with specific biological
activity of the proteins as cell migration, proliferation, or differentiation. Overexpression or
constitutive dimerization (due notably to mutations) of these transmembrane receptors
are involved in several physiopathological contexts as cancers. The transmembrane
domain of tyrosine kinase receptors as ErbB family proteins (implicated in several
cancers as HER2 in breast cancer) or other receptors as Neuropilins has been described
these last years as a target to inhibit their dimerization/activation using several strategies.
In this review, we will focus on the strategy which consists in using peptides to disturb in
a specific manner the interactions between transmembrane domains and the signaling
pathways (induced by ligand binding) of these receptors involved in cancer. This
approach can be extended to inhibit other transmembrane protein dimerization as
neuraminidase-1 (the catalytic subunit of elastin receptor complex), Discoidin Domain
Receptor 1 (a tyrosine kinase receptor activated by type I collagen) or G-protein coupled
receptors (GPCRs) which are involved in cancer processes.

Keywords: рак, protein-protein interactions, белок-белковые взаимодействия, cancer, transmembrane peptides, transmembrane protein dimerization inhibition, peptide delivery strategy, трансмембранные пептиды, ингибирование димеризации трансмембранного белка, стратегия доставки пептидов