Abstract
Accumulating evidence suggests that alteration of subcellular protein localization and compartmentalization results in various types of cancer. Since the receptor tyrosine kinases (RTKs) are highly expressed and activated in human malignancies and frequently correlated with poor prognosis, it is critical to understand subcellular trafficking of the RTKs, such as the epidermal growth factor receptor (EGFR) family. A novel nuclear mode of EGFR signaling has been gradually deciphered, in which EGFR is shuttled from the cell surface to the nucleus after endocytosis. Nuclear EGFR acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, DNA repair and replication, and chemo- and radio-resistance. In this chapter, we summarize the functions of nuclear EGFR family and the potential pathways by which cell surface EGFR is trafficked to a variety of intracellular organelles such as the Golgi apparatus, the endoplasmic reticulum, the mitochondria, as well as the nucleus. Understanding the molecular mechanism of EGFR trafficking will contribute to both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application.
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