EGFR signaling pathway in breast cancers: From traditional signal transduction to direct nuclear translocalization

  • Lo H
  • Hsu S
  • Hung M
  • 96


    Mendeley users who have this article in their library.
  • 141


    Citations of this article.


Aberrant epidermal growth factor receptor (EGFR) signaling is a major characteristic of many human malignancies including breast cancer. Since the discovery of EGF in 1960's and its receptor in 1980's, our understanding of the EGF/EGFR pathway has been significantly advanced and consequently, EGFR is considered as a major oncogenic factor and an attractive therapeutic target. The well-established traditional function of EGFR is known to transmit extra-cellular mitogenic signals, such as EGF and transforming growth factor-alpha (TGF-alpha), through activating a number of downstream signaling cascades. These include signaling modules that involve phospholipase C-gamma, Ras, and phosphatidylinositol-3 kinase (PI-3K). In cancer cells, the common outcomes following the activation of the EGFR-mediated downstream pathways are altered gene activities, leading to un-controlled tumor proliferation and apoptosis. Interestingly, emerging evidences suggest the existence of a direct mode of the EGFR pathway that is distinct from the traditional transduction pathway. This new mode of EGFR signaling involves cellular transport of EGFR from the cell-surface to the cell nucleus, association of nuclear EGFR complex with gene promoters, and transcriptional regulation of the target genes. Although the nature and pathological consequences of the nuclear EGFR pathway remain elusive, accumulating evidences suggest its association with increased tumor cell proliferation and poor survival rate in breast cancer patients. While several anti-EGFR agents are being tested in breast cancer patients clinically and others under pre-clinical development, a better understanding of the traditional and the nuclear EGFR pathways will facilitate the identification of patients that are likely to respond to these agents as well as future development of more effective anti-EGFR therapeutic interventions.

Author-supplied keywords

  • Breast cancer
  • Epithelial growth factor receptor (EGFR)
  • STAT3
  • Transcriptional regulation

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Hui Wen Lo

  • Sheng Chieh Hsu

  • Mien Chie Hung

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free