[Nuclear EGFR: a new mode of oncogenic signalling in cancer]

EGFR (Epidermal Growth Factor Receptor) is one of the most studied molecules in biology. From its early identification and cloning to the discovery of its role in cancer, it has been at the forefront of our understanding of Receptor Tyrosine Kinase (RTK) and cell signals that induce homeostasis, but when overexpressed, facilitate tumorigenesis. While the biological functions of EGFR traditionally involve the activation of a signaling network from the plasma membrane that includes activation of the RAS/MAPK/ERK, PI3K/AKT and STATS pathways, a new mode of EGFR signaling has been progressively decoded in which membrane-associated EGFR is transported after endocytosis from cell surface to the nucleus through endocytosis, retrograde trafficking to the Golgi, the endoplasmic reticulum and the inner nuclear membrane through a series of proteic interactions. In the nucleus, EGFR acts as a transcriptional regulator, a kinase and a physical interactor, transmits signals and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and resistance to cancer therapies. In this review, we will summarize current knowledge of the EGFR nuclear signaling network, including how it is delivered to the nucleus, the functions it serves in the nucleus and how these functions affect cancer progression, survival and the response to treatment.