New Mode of Growth Factor Signaling

Mutations that increase the expression or activity of the epidermal growth factor receptor (EGFR) are associated with several cancer types. Seven different growth factors, also called ligands, bind to EGFR and have three recognized modes of signaling – autocrine, paracrine and juxtacrine.

Robert Coffey, M.D., and colleagues have identified a new mode of EGFR ligand signaling via exosomes – small (30-90nm) membrane-bound vesicles – and have dubbed this new mode of growth factor signaling extracrine (exosomal targeted receptor activation). They show that human breast and colorectal cancer cells release exosomes containing full-length, signaling-competent EGFR ligands. Exosomes containing the ligand amphiregulin increased invasiveness of breast cancer cells 4-fold over exosomes containing two other EGFR ligands (TGF-α and HB-EGF).

The findings, published in Current Biology, suggest that this new mode of EGFR ligand signaling could have important implications for cancer invasion, metastasis and the tendency of cancer cells to cause changes to normal cells that surround them (cancer field effect).