Regulation of epidermal growth factor receptor signaling by endocytosis in normal and malignant cells

Sergio Anastasi, Stefano Alemà, Oreste Segatto

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose physiological signaling activity regulates the morphogenesis and homeostasis of several tissues from worms to man. In contrast, aberrant signaling caused by overexpression or mutational activation of the EGFR plays a causal role in the pathogenesis of a number of human tumors. The fidelity of EGFR signals, which must be robust enough to convey instructive cues to the cell while also preventing the threat posed by excess receptor activity, is guaranteed by a complex regulatory circuitry. A pervasive role in EGFR regulation is played by endocytosis. Owing to its capacity to instruct degradation of activated EGFRs and reduce receptor expression at the cell surface, endocytosis has been regarded historically as the main cellular mechanism deputed to the attenuation of EGFR signaling. More recently, a great deal of attention has been focused on understanding endocytosis also as an element of spatial regulation of EGFR activity. Herein, we discuss molecular mechanisms controlling EGFR endocytosis, as they relate to the regulation of EGFR signal output and the implementation of EGFR-driven biological programs. We will then focus on reviewing the variegated mechanisms through which the EGFR escapes from downregulation in cancer cells. The emerging picture assigns to faulty endocytosis, in concert with constitutive catalytic activation, a prominent role in the ominous oncogenic conversion of EGFR.

Original languageEnglish
Title of host publicationVesicle Trafficking in Cancer
PublisherSpringer New York
Pages279-302
Number of pages24
Volume9781461465287
ISBN (Print)9781461465287, 1461465273, 9781461465270
DOIs
Publication statusPublished - Jul 1 2013

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Anastasi, S., Alemà, S., & Segatto, O. (2013). Regulation of epidermal growth factor receptor signaling by endocytosis in normal and malignant cells. In Vesicle Trafficking in Cancer (Vol. 9781461465287, pp. 279-302). Springer New York. https://doi.org/10.1007/978-1-4614-6528-7_14