title: Non-canonical signaling mode of the epidermal growth factor receptor family.
abstract: Epidermal growth factor receptor (EGFR) and its family members are key players in both physiological and pathological settings for which they are well recognized as models for investigating the functions and regulations of other membrane receptor tyrosine kinases (RTKs) and serve as therapeutic targets critical to clinical need and fundamental research. The canonical view of the pivotal functions in the EGFR family has been well documented as being an initiator of signaling amplification cascades from the plasma membrane to different subcellular compartments via receptor endocytic trafficking, intermolecular interaction, and kinase-substrate reaction in a temporalspatial manner. However, several lines of evidence have identified non-canonical roles of the EGFR family, acting as a transcriptional factor and a chromatin regulator in the nucleus to regulate gene expression, DNA replication, and DNA damage repair. Moreover, the EGFR family can even exert its impact outside the host cell through exosomal vesicle secretion. The emerging concept of the non-canonical roles of the EGFR family reveals an astonishing and elaborate scheme on the molecular functions of membrane RTKs, offering new insights into the receptor biology as well as the development of comprehensive therapeutic strategies in the future.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston 77030, TX, USA.
authors.forename: Heng-Huan
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston 77030, TX, USA ; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University Taichung 404, Taiwan.
authors.forename: Ying-Nai
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston 77030, TX, USA ; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University Taichung 404, Taiwan ; The University of Texas Graduate School of Biomedical Sciences at Houston Houston 77030, TX, USA ; Department of Biotechnology, Asia University Taichung 413, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
keywords: EGFR family; exosomal secretion; nuclear function; nuclear translocation; vesicle membrane-associated pathways